WO2024102702A2 - Methods and materials for assessing and treating cutaneous squamous cell carcinoma - Google Patents

Methods and materials for assessing and treating cutaneous squamous cell carcinoma Download PDF

Info

Publication number
WO2024102702A2
WO2024102702A2 PCT/US2023/078902 US2023078902W WO2024102702A2 WO 2024102702 A2 WO2024102702 A2 WO 2024102702A2 US 2023078902 W US2023078902 W US 2023078902W WO 2024102702 A2 WO2024102702 A2 WO 2024102702A2
Authority
WO
WIPO (PCT)
Prior art keywords
polypeptide
mrna encoding
altered level
level
altered
Prior art date
Application number
PCT/US2023/078902
Other languages
French (fr)
Other versions
WO2024102702A3 (en
WO2024102702A9 (en
Inventor
Aaron R. MANGOLD
Xing Li
Nan Zhang
Original Assignee
Mayo Foundation For Medical Education And Research
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Mayo Foundation For Medical Education And Research filed Critical Mayo Foundation For Medical Education And Research
Publication of WO2024102702A2 publication Critical patent/WO2024102702A2/en
Publication of WO2024102702A3 publication Critical patent/WO2024102702A3/en
Publication of WO2024102702A9 publication Critical patent/WO2024102702A9/en

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/158—Expression markers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2458/00—Labels used in chemical analysis of biological material
    • G01N2458/10—Oligonucleotides as tagging agents for labelling antibodies

Definitions

  • methods and materials provided herein can be used to identify a mammal (e.g., a human) having a cSCC as being likely to experience a prolonged survival from cSCC.
  • methods and materials provided herein can be used to determine whether or not a cSCC is likely to metastasize (e.g., likely to metastasize to one or more lymph nodes).
  • This document also provides methods and materials for treating a mammal (e.g., a human) having a cSCC where the treatment is selected based, at least in part, on the predicted survival of the mammal and/or whether or not the cSCC is likely to metastasize.
  • Non-melanoma skin cancers most of which are basal cell carcinoma (BCC) and cSCC, are the most common cancer in humans, and the fifth most costly (Guy et al., Am. J. Prev. Med., 48(2):183-187 (2015); Rogers et al., JAMA Dermatol., 151(10):1081-1086 (2015); and Housman et al., J. Am. Acad. Dermatol., 48(3):425-429 (2003)).
  • BCC basal cell carcinoma
  • cSCC basal cell carcinoma
  • cSCC can be cured with surgery, but metastasis occurs in up to 5% of patients, and metastatic cSCC carries a poor 5-year survival of only 25-35% (Karia et al., J. Am. Acad. Dermatol.,68(6):957-966 (2013)).
  • SUMMARY This document provides methods and materials for assessing and/or treating cSCC.
  • this document provides methods and materials for determining whether or not a Attorney Docket No.07039-2153WO1 / 2022-168 mammal (e.g., a human) having a cSCC is likely to experience a prolonged survival from cSCC and/or whether the cSCC is likely to metastasize (e.g., likely to metastasize to one or more lymph nodes).
  • a sample e.g., a tissue sample containing one or more cSCC cells
  • a mammal having a cSCC can be assessed to determine if the mammal is likely to experience a prolonged survival from cSCC and/or whether the cSCC is likely to metastasize (e.g., likely to metastasize to one or more lymph nodes) based, at least in part, on the molecular signature of the cSCC.
  • a sample e.g., a tissue sample containing one or more cSCC cells obtained from a mammal having a cSCC can be assessed for the presence or absence of altered levels (e.g., increased levels or decreased levels) of one or more (e.g., one, two, three, four, five, six, seven, or more) polypeptides (or mRNA encoding such polypeptides) to determine whether or not that mammal is likely to experience prolonged survival from cSCC (e.g., prolonged survival from the time of cSCC diagnosis) and/or whether that cSCC is likely to metastasize.
  • altered levels e.g., increased levels or decreased levels
  • This document also provides methods and materials for treating a mammal (e.g., a human) having a cSCC where the treatment is selected based, at least in part, on the predicted survival of the mammal and/or whether or not the cSCC is likely to metastasize.
  • a mammal e.g., a human
  • a mammal having a cSCC can be administered one or more cancer treatments that are selected based, at least in part, on the molecular signature of the cSCC.
  • a baculoviral IAP repeat- containing protein 5 polypeptide
  • a maternal embryonic leucine zipper kinase MELK
  • a maternal embryonic leucine zipper kinase MELK
  • an altered level of an interferon epsilon (IFNE) polypeptide or mRNA encoding an IFNE polypeptide
  • an altered level of a hydroxymethylglutaryl-CoA synthase cytoplasmic (HMGCS1) polypeptide (or mRNA encoding a HMGCS1 polypeptide)
  • an altered level of an ankyrin-2 (ANK2) polypeptide or mRNA encoding an ANK2 polypeptide
  • an altered level of a laminin subunit alpha-2 LAMA2 polypeptide
  • an altered level of a laminin subunit alpha-2 LAMA2 polypeptide
  • a chondrosarcoma-associated gene 1 (CSAG1) polypeptide (or mRNA encoding a CSAG1 polypeptide), an altered level of an ubiquitin-conjugating enzyme E2 C (UBE2C) polypeptide (or mRNA encoding an UBE2C polypeptide), an altered level of an ankyrin repeat domain-containing protein 1 (ANKRD1) polypeptide (or mRNA encoding an ANKRD1 polypeptide), an altered level of a CUB and sushi domain-containing protein 3 (CSMD3) polypeptide (or mRNA encoding a CSMD3 polypeptide), an altered level of a topoisomerase 2-alpha (TOP2A) polypeptide (or mRNA encoding a TOP2A polypeptide), an altered level of a targeting protein for Xklp2 (TPX2) polypeptide (or mRNA encoding a TPX2 polypeptide),
  • ZNF750 zinc finger protein 750
  • CDCA5 cell division cycle-associated 5
  • CXCL8 C-X-C motif chemokine ligand 8
  • PRC1 protein regulator of cytokinesis 1
  • KRT2 keratin 2
  • an altered level of an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide), an altered level of a CDCA5 polypeptide (or mRNA encoding a CDCA5 polypeptide), an altered level of a CXCL8 polypeptide (or mRNA encoding a CXCL8 polypeptide), an altered level of a PRC1 polypeptide (or mRNA encoding a PRC1 polypeptide), an altered level of a KRT2 polypeptide (or mRNA encoding Attorney Docket No.07039-2153WO1 / 2022-168 a KRT2 polypeptide), an altered level of an ALOX12 polypeptide (or mRNA encoding an ALOX12 polypeptide), an altered level of an ALDH3A2 polypeptide (or mRNA encoding an ALDH3A2 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding
  • an altered level of a ZNF750 polypeptide or mRNA encoding a ZNF750 polypeptide
  • an altered level of a CDCA5 polypeptide or mRNA encoding a CDCA5 polypeptide
  • an altered level of an ALOX12 polypeptide or mRNA encoding a ALOX12 polypeptide
  • an altered level of an ALDH3A2 polypeptide or mRNA encoding an ALDH3A2 polypeptide
  • an altered level of a DMD polypeptide or mRNA encoding a DMD polypeptide
  • an altered level of a NQO1 polypeptide or mRNA encoding a NQO1 polypeptide
  • an altered level of an ALDH1A1 polypeptide or mRNA encoding an ALDH1A1 polypeptide
  • an altered level of a cell division cycle 6 (CDC6) polypeptide or mRNA encoding a CDC6 polypeptide
  • KIT KIT proto-oncogene
  • CYP2U1 cytochrome P450 family 2 subfamily U member 1
  • ZNF750 polypeptide
  • DMD polypeptide or mRNA encoding a DMD polypeptide
  • CYP4F3 or mRNA encoding a CYP4F3 polypeptide
  • CALCOCO1 polypeptide
  • CASP14 or mRNA encoding a CALCOCO1 polypeptide
  • CASP14 or mRNA encoding a Attorney Docket No.07039-2153WO1 /
  • an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of a FN1 polypeptide (or mRNA encoding a FN1 polypeptide), an altered level of a MGAM polypeptide (or mRNA encoding a MGAM polypeptide), an altered level of an EVPL polypeptide (or mRNA encoding an EVPL polypeptide), an altered level of an AOX1 polypeptide (or mRNA encoding an AOX1 polypeptide), an altered level of a PLA2R1 polypeptide (or mRNA encoding a PLA2R1 polypeptide), an altered level of a TRPM1 polypeptid
  • a mammal having a high-risk cSCC e.g., a cSCC that is identified as being likely to metastasize as described herein
  • a mammal having a low-risk cSCC can forgo unnecessary treatments (e.g., sentinel lymph node biopsies (SLNBs) and complete lymph node dissections (CLNDs)) and be spared from the risks and complications associated with some treatments (e.g., SLNBs and CLNDs).
  • SLNBs sentinel lymph node biopsies
  • CLNDs complete lymph node dissections
  • SLNBs and CLNDs complete lymph node dissections
  • the methods can include, or consist essentially of, (a) determining if a sample from a mammal having a cSCC contains the presence or absence of at least one of (1) an altered level of a BIRC5 polypeptide or mRNA encoding a BIRC5 polypeptide, (2) an altered level of a MELK polypeptide or mRNA encoding a MELK polypeptide, (3) an altered level of an IFNE polypeptide or mRNA encoding an IFNE polypeptide, (4) an altered level of a HMGCS1 polypeptide or mRNA encoding a HMGCS1 polypeptide, (5) an altered level of an ANK2 polypeptide or mRNA encoding an ANK2 polypeptide, (6) an altered level of a LAMA2 polypeptide or mRNA encoding a LAMA2 polypeptide, (7) an altered level of a CYP2U1 polypeptide or mRNA encoding a CYP2U1 polypeptide
  • the mammal can be a human.
  • the presence or absence of the altered level of the BIRC5 polypeptide can be determined.
  • the presence or absence of the altered level of the MELK polypeptide can be determined.
  • the presence or absence of the altered level of the IFNE polypeptide can be determined.
  • the presence or absence of the altered level of the HMGCS1 polypeptide can be determined.
  • the presence or absence of the altered level of the ANK2 polypeptide can be determined.
  • the presence or absence of the altered level of the LAMA2 polypeptide can be determined.
  • the presence or absence of the altered level of the CYP2U1 polypeptide can be determined.
  • the presence or absence of the altered level of the FAM13C polypeptide can be determined.
  • the presence or absence of the altered level of the COL25A1 polypeptide can be determined.
  • the presence or absence of the altered level of the TG polypeptide can be determined.
  • the presence or absence of the altered level of the FAT4 polypeptide can be determined.
  • the sample can be a tissue sample comprising a cSCC cell.
  • the methods can include, or consist essentially of, (a) determining if a sample from a mammal having a cSCC contains the presence or absence of at least one of (1) an altered level of a CSAG1 polypeptide or mRNA encoding a CSAG1 polypeptide, (2) an altered level of an UBE2C polypeptide or mRNA encoding an UBE2C polypeptide, (3) an altered level of an ANKRD1 polypeptide or mRNA encoding an ANKRD1 polypeptide, (4) an altered level of a CSMD3 polypeptide or mRNA encoding a CSMD3 polypeptide, (5) an altered level of a TOP2A polypeptide or mRNA encoding a TOP2A polypeptide, (6) an altered level of a TPX2 polypeptide or mRNA encoding a TPX2 polypeptide, (7) an altered level of a KSR2 polypeptide or mRNA encoding a KSR2 poly
  • the mammal can be a human.
  • the presence or absence of the altered level of the CSAG1 polypeptide can be determined.
  • the presence or absence of the altered level of the UBE2C polypeptide can be determined.
  • the presence or absence of the altered level of the ANKRD1 polypeptide can be determined.
  • the presence or absence of the altered level of the CSMD3 polypeptide can be determined.
  • the presence or absence of the altered level of the TOP2A polypeptide can be determined.
  • the presence or absence of the altered level of the TPX2 polypeptide can be determined.
  • the presence or absence of the altered level of the KSR2 polypeptide can be determined.
  • the presence or absence of the altered level of the CSMD2 polypeptide is determined.
  • the presence or absence of the altered level of the MMP20 polypeptide is Attorney Docket No.07039-2153WO1 / 2022-168 determined.
  • the presence or absence of the altered level of the PCSK1 polypeptide can be determined.
  • the presence or absence of the altered level of the TMEM150B polypeptide can be determined.
  • the presence or absence of the altered level of the ACSL1 polypeptide can be determined.
  • the presence or absence of the altered level of the TSGA10 polypeptide can be determined.
  • the presence or absence of the altered level of the KIT polypeptide can be determined.
  • the presence or absence of the altered level of the RGL3 polypeptide can be determined.
  • the presence or absence of the altered level of the PLA2G6 polypeptide can be determined.
  • the sample can be a tissue sample comprising a cSCC cell.
  • this document features methods for selecting a treatment for a mammal having a cSCC.
  • the methods can include, or consist essentially of, (a) determining that a sample from a mammal having a cSCC contains: the absence of (a-1) an altered level of a BIRC5 polypeptide or mRNA encoding a BIRC5 polypeptide, (a-2) an altered level of a MELK polypeptide or mRNA encoding a MELK polypeptide, (a-3) an altered level of an IFNE polypeptide or mRNA encoding an IFNE polypeptide, (a-4) an altered level of a HMGCS1 polypeptide or mRNA encoding a HMGCS1 polypeptide, (a-5) an altered level of an ANK2 polypeptide or mRNA encoding an ANK2 polypeptide, (a-6) an altered level of a LAMA2
  • the mammal can be a human.
  • the adjuvant therapy can include radiation therapy.
  • the adjuvant therapy can include administering an anti-cancer drug to the mammal.
  • the anti-cancer can becemiplimab-rwlc, nivolumab, ipilimumab, pembrolizumab, talimogene laherparepvec, cetuximab, capecitabine, carboplatin, or fluorouracil (5-FU).
  • this document features methods for selecting a treatment for a mammal having a cSCC.
  • the methods can include, or consist essentially of, (a) determining that a sample from a mammal having a cSCC contains: the presence of at least one of (a-1) an altered level of a BIRC5 polypeptide or mRNA encoding a BIRC5 polypeptide, (a-2) an altered level of a MELK polypeptide or mRNA encoding a MELK polypeptide, (a-3) an altered level of an IFNE polypeptide or mRNA encoding an IFNE polypeptide, (a-4) an altered level of a HMGCS1 polypeptide or mRNA encoding a HMGCS1 polypeptide, (a-5) an altered level of an ANK2 polypeptide or mRNA encoding an ANK2 polypeptide, (a-6) an altered level of a LAMA2 polypeptide or mRNA encoding a LAMA2 polypeptide, (a-7) an altered level of a CYP2U1 polypeptide or m
  • the mammal can be a human.
  • the adjuvant therapy can include radiation therapy.
  • the adjuvant therapy can include administering an anti-cancer drug to the mammal.
  • the anti-cancer can becemiplimab-rwlc, nivolumab, ipilimumab, pembrolizumab, talimogene laherparepvec, cetuximab, capecitabine, carboplatin, or 5-FU.
  • this document features methods for treating a mammal having a cSCC.
  • the methods can include, or consist essentially of, (a) determining that a sample from a mammal having a cSCC contains: the absence of (a-1) an altered level of a BIRC5 polypeptide or mRNA encoding a BIRC5 polypeptide, (a-2) an altered level of a MELK polypeptide or mRNA encoding a MELK polypeptide, (a-3) an altered level of an IFNE polypeptide or mRNA encoding an IFNE polypeptide, (a-4) an altered level of a HMGCS1 polypeptide or mRNA encoding a HMGCS1 polypeptide, (a-5) an altered level of an ANK2 polypeptide or mRNA encoding an ANK2 polypeptide, (a-6) an altered level of a LAMA2 polypeptide or mRNA encoding a LAMA2 polypeptide, (a-7) an altered level of a CYP2U1 polypeptide or mRNA encoding
  • the mammal can be a human.
  • the sample can be a tissue sample comprising a cSCC cell.
  • the adjuvant therapy can include radiation therapy.
  • the adjuvant therapy can include administering an anti-cancer drug to the mammal.
  • the anti-cancer can be cemiplimab-rwlc, nivolumab, ipilimumab, pembrolizumab, talimogene laherparepvec, cetuximab, capecitabine, carboplatin, or 5-FU.
  • this document features methods for treating a cSCC.
  • the methods can include, or consist essentially of, subjecting a mammal identified as having a sample comprising (a) or (b) to a surgery to remove the cSCC and administering an adjuvant therapy to the mammal, where (a) comprises the absence of (a-1) an altered level of a BIRC5 Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide or mRNA encoding a BIRC5 polypeptide, (a-2) an altered level of a MELK polypeptide or mRNA encoding a MELK polypeptide, (a-3) an altered level of an IFNE polypeptide or mRNA encoding an IFNE polypeptide, (a-4) an altered level of a HMGCS1 polypeptide or mRNA encoding a HMGCS1 polypeptide, (a-5) an altered level of an ANK2 polypeptide or mRNA encoding an ANK2 polypeptide, (a-6) an altered level of a L
  • the mammal can be a human.
  • the sample can be a tissue sample comprising a cSCC cell.
  • the adjuvant therapy can include radiation therapy.
  • the adjuvant therapy can include administering an anti-cancer drug Attorney Docket No.07039-2153WO1 / 2022-168 to the mammal.
  • the anti-cancer can be cemiplimab-rwlc, nivolumab, ipilimumab, pembrolizumab, talimogene laherparepvec, cetuximab, capecitabine, carboplatin, or 5-FU.
  • this document features methods for treating a mammal having a cSCC.
  • the methods can include, or consist essentially of, (a) determining if a sample from a mammal having a cSCC comprises: the presence of at least one of (a-1) an altered level of a BIRC5 polypeptide or mRNA encoding a BIRC5 polypeptide, (a-2) an altered level of a MELK polypeptide or mRNA encoding a MELK polypeptide, (a-3) an altered level of an IFNE polypeptide or mRNA encoding an IFNE polypeptide, (a-4) an altered level of a HMGCS1 polypeptide or mRNA encoding a HMGCS1 polypeptide, (a-5) an altered level of an ANK2 polypeptide or mRNA encoding an ANK2 polypeptide, (a-6) an altered level of a LAMA2 polypeptide or mRNA encoding a LAMA2 polypeptide, (a-7) an altered level of a CYP2U1 polypeptide or
  • the mammal can be a human.
  • the sample can be a tissue sample comprising a cSCC cell.
  • the adjuvant therapy can include radiation therapy.
  • the adjuvant therapy can include administering an anti-cancer drug to the mammal.
  • the anti-cancer drug can be cemiplimab- rwlc, nivolumab, ipilimumab, pembrolizumab, talimogene laherparepvec, cetuximab, capecitabine, carboplatin, or 5-FU.
  • this document features methods for treating cSCC.
  • the methods can include, or consist essentially of, subjecting a mammal identified as comprising a sample comprising (a) or (b) to a surgery to remove the cSCC in the absence of an adjuvant therapy, where (a) comprises the presence of at least one of (a-1) an altered level of a BIRC5 polypeptide or mRNA encoding a BIRC5 polypeptide, (a-2) an altered level of a MELK polypeptide or mRNA encoding a MELK polypeptide, (a-3) an altered level of an IFNE polypeptide or mRNA encoding an IFNE polypeptide, (a-4) an altered level of a HMGCS1 polypeptide or mRNA encoding a HMGCS1 polypeptide, (a-5) an altered level of an ANK2 polypeptide or mRNA encoding an ANK2 polypeptide, (a-6) an altered level of a LAMA2 polypeptide or mRNA encoding a LAMA2 poly
  • the mammal can be a human.
  • the sample can be a tissue sample comprising a cSCC cell.
  • the adjuvant therapy can include radiation therapy.
  • the adjuvant therapy can include administering an anti-cancer drug to the mammal.
  • the anti- cancer drug can be cemiplimab-rwlc, nivolumab, ipilimumab, pembrolizumab, talimogene laherparepvec, cetuximab, capecitabine, carboplatin, or 5-FU.
  • this document features methods for assessing a mammal having a cSCC where the methods can include, or consist essentially of, (a) determining if a sample from the mammal contains the presence or absence of at least one of (1) an altered level of an ACSL1 polypeptide or mRNA encoding an ACSL1 polypeptide, (2) an altered level of an ALDH1A1 polypeptide or mRNA encoding an ALDH1A1 polypeptide, (3) an altered level of an ALDH3A2 polypeptide or mRNA encoding an ALDH3A2 polypeptide, (4) an altered level of an ALOX12 polypeptide or mRNA encoding an ALOX12 polypeptide, (5) an altered level of a CALCOCO1 polypeptide or mRNA encoding an CALCOCO1 polypeptide, (6) an altered level of a CASP14 polypeptide or mRNA encoding an CASP14 polypeptide, (7) an altered level of a CDC6 polypeptide
  • the mammal can be a human.
  • the presence or absence of the altered level of the ACSL1 polypeptide can be determined.
  • the presence or absence of the altered level of the ALDH1A1 polypeptide can be determined.
  • the presence or absence of the altered level of the ALDH3A2 polypeptide can be determined.
  • the presence or absence of the altered level of the ALOX12 polypeptide can be determined.
  • the presence or absence of the altered level of the CALCOCO1 polypeptide can be determined.
  • the presence or absence of the altered level of the CASP14 polypeptide can be determined.
  • the presence or absence of the altered level of the CDC6 polypeptide can be determined.
  • the presence or absence of the altered level of the CDCA5 polypeptide can be determined.
  • the presence or absence of the altered level of the CEP55 polypeptide can be determined.
  • the presence or absence of the altered level of the CXCL8 polypeptide can be determined.
  • the presence or absence of the altered level of the CYP4F3 polypeptide can be determined.
  • the presence or absence of the altered level of the DMD polypeptide can be determined.
  • the presence or absence of the altered level of the KRT2 polypeptide can be determined.
  • the presence or absence of the altered level of the NQO1 polypeptide can be determined.
  • the presence or absence of the altered level of the PRC1 polypeptide can be determined.
  • the presence or absence of the altered level of the TSGA10 polypeptide can be determined.
  • the presence or absence of the altered level of the ZNF750 polypeptide can be determined.
  • the sample can be a tissue sample including a cSCC cell.
  • this document features methods for assessing a mammal having a cSCC where the methods can include, or consist essentially of, (a) determining if a sample from the mammal contains the presence or absence of at least one of (1) an altered level of an aldehyde oxidase 1 (AOX1) polypeptide or mRNA encoding an AOX1 polypeptide, (2) an altered level of a calcium binding and coiled-coil domain 1 (CALCOCO1) polypeptide or Attorney Docket No.07039-2153WO1 / 2022-168 mRNA encoding an CALCOCO1 polypeptide, (3) an altered level of a caspase 14 (CASP14) polypeptide or mRNA encoding an CASP14 polypeptide, (4) an altered level of a cell division cycle 6 (CDC6) polypeptide or mRNA encoding an CDC6 polypeptide, (5) an altered level of a a
  • the mammal can be a human.
  • the presence or absence of the altered level of the AOX1 polypeptide can be determined.
  • the presence or absence of the altered level of the CALCOCO1 polypeptide can be determined.
  • the presence or absence of the altered level of the CASP14 polypeptide can be determined.
  • the presence or absence of the altered level of the CDC6 polypeptide can be determined.
  • the presence or absence of the altered level of the CERS3 polypeptide can be determined.
  • the presence or absence of the Attorney Docket No.07039-2153WO1 / 2022-168 altered level of the CYP2E1 polypeptide can be determined.
  • the presence or absence of the altered level of the CYP2U1 polypeptide can be determined.
  • the presence or absence of the altered level of the CYP4F22 polypeptide can be determined.
  • the presence or absence of the altered level of the CYP4F3 polypeptide can be determined.
  • the presence or absence of the altered level of the DMD polypeptide can be determined.
  • the presence or absence of the altered level of the EVPL polypeptide can be determined.
  • the presence or absence of the altered level of the FASN polypeptide can be determined.
  • the presence or absence of the altered level of the FN1 polypeptide can be determined.
  • the presence or absence of the altered level of the KIT polypeptide can be determined.
  • the presence or absence of the altered level of the MGAM polypeptide can be determined.
  • the presence or absence of the altered level of the PLA2R1 polypeptide can be determined.
  • the presence or absence of the altered level of the TRPM1 polypeptide can be determined.
  • the presence or absence of the altered level of the ZNF750 polypeptide can be determined.
  • the sample can be a tissue sample including a cSCC cell.
  • this document features methods for selecting a treatment for a mammal having a cSCC where the methods can include, or consist essentially of, (a) determining that a sample from the mammal contains: the absence of (a-1) an altered level of an ACSL1 polypeptide or mRNA encoding an ACSL1 polypeptide, (a-2) an altered level of an ALDH1A1 polypeptide or mRNA encoding an ALDH1A1 polypeptide, (a-3) an altered level of an ALDH3A2 polypeptide or mRNA encoding an ALDH3A2 polypeptide, (a-4) an altered level of an ALOX12 polypeptide or mRNA encoding an ALOX12 polypeptide, (a-5) an altered level of
  • the mammal can be a human.
  • the adjuvant therapy can include radiation therapy.
  • the adjuvant therapy can include administering an anti-cancer drug to the mammal.
  • the anti- cancer drug can be cemiplimab-rwlc, nivolumab, ipilimumab, pembrolizumab, talimogene laherparepvec, cetuximab, capecitabine, carboplatin, or 5-FU.
  • this document features methods for selecting a treatment for a mammal having a cSCC where the methods can include, or consist essentially of, (a) determining that a sample from the mammal contains: the presence of at least one of (a-1) an altered level of an ACSL1 polypeptide or mRNA encoding an ACSL1 polypeptide, (a-2) an altered level of an ALDH1A1 polypeptide or mRNA encoding an ALDH1A1 polypeptide, (a- 3) an altered level of an ALDH3A2 polypeptide or mRNA encoding an ALDH3A2 polypeptide, (a-4) an altered level of an ALOX12 polypeptide or mRNA encoding an ALOX12 polypeptide, (a-5) an altered level of a CALCOCO1 polypeptide or mRNA encoding a CALCOCO1 polypeptide, (a-6) an altered level of
  • the mammal can be a human.
  • the adjuvant therapy can include radiation therapy.
  • the adjuvant therapy can include administering an anti-cancer drug to the mammal.
  • the anti- cancer drug can be cemiplimab-rwlc, nivolumab, ipilimumab, pembrolizumab, talimogene laherparepvec, cetuximab, capecitabine, carboplatin, or 5-FU.
  • this document features methods for treating a mammal having a cSCC where the methods can include, or consist essentially of, (a) determining that a sample from the mammal contains: the absence of (a-1) an altered level of an ACSL1 polypeptide or mRNA encoding an ACSL1 polypeptide, (a-2) an altered level of an ALDH1A1 polypeptide or mRNA encoding an ALDH1A1 polypeptide, (a-3) an altered level of an ALDH3A2 polypeptide or mRNA encoding an ALDH3A2 polypeptide, (a-4) an altered level of an ALOX12 polypeptide or mRNA encoding an ALOX12 polypeptide, (a-5) an altered level of a CALCOCO1 polypeptide or mRNA encoding a CALCOCO1 polypeptide, (a-6) an altered level of a CASP14 polypeptide or mRNA encoding a CASP14 polypeptide, (a-7)
  • the mammal can be a human.
  • the sample can be a tissue sample including a cSCC cell.
  • the adjuvant therapy can include radiation therapy.
  • the adjuvant therapy can include administering an anti-cancer drug to the mammal.
  • the anti-cancer drug can be cemiplimab-rwlc, nivolumab, ipilimumab, pembrolizumab, talimogene laherparepvec, cetuximab, capecitabine, carboplatin, or 5-FU.
  • this document features methods for treating a cSCC where the methods can include, or consist essentially of, subjecting a mammal identified as having a sample including (a) or (b) to a surgery to remove the cSCC and administering an adjuvant therapy to the mammal, where the (a) includes the absence of (a-1) an altered level of an ACSL1 polypeptide or mRNA encoding an ACSL1 polypeptide, (a-2) an altered level of an ALDH1A1 polypeptide or mRNA encoding an ALDH1A1 polypeptide, (a-3) an altered level of an ALDH3A2 polypeptide or mRNA encoding an ALDH3A2 polypeptide, (a-4) an altered level of an ALOX12 polypeptide or mRNA encoding an ALOX12 polypeptide, (a-5) an altered level of a CALCOCO1 polypeptide or mRNA
  • the mammal can be a human.
  • the sample can be a tissue sample including a cSCC cell.
  • the adjuvant therapy can include radiation therapy.
  • the adjuvant therapy can include administering an anti-cancer drug to the mammal.
  • the anti-cancer drug can be cemiplimab-rwlc, nivolumab, ipilimumab, pembrolizumab, talimogene laherparepvec, cetuximab, capecitabine, carboplatin, or 5-FU.
  • this document features methods for treating a mammal having a cSCC where the methods can include, or consist essentially of, (a) determining if a sample from the mammal includes: the presence of at least one of (a-1) an altered level of an ACSL1 polypeptide or mRNA encoding an ACSL1 polypeptide, (a-2) an altered level of an ALDH1A1 polypeptide or mRNA encoding an ALDH1A1 polypeptide, (a-3) an altered level of an ALDH3A2 polypeptide or mRNA encoding an ALDH3A2 polypeptide, (a-4) an altered level of an ALOX12 polypeptide or mRNA encoding an ALOX12 polypeptide, (a-5) an altered level of a CALCOCO1 polypeptide or mRNA encoding a CALCOCO1 polypeptide, (a-6) an altered level of a CASP14 polypeptide or mRNA encoding a CASP14 polypeptide
  • the mammal can be a human.
  • the sample can be a tissue sample including a cSCC cell.
  • the adjuvant therapy can include radiation Attorney Docket No.07039-2153WO1 / 2022-168 therapy.
  • the adjuvant therapy can include administering an anti-cancer drug to the mammal.
  • the anti-cancer drug can be cemiplimab-rwlc, nivolumab, ipilimumab, pembrolizumab, talimogene laherparepvec, cetuximab, capecitabine, carboplatin, or 5-FU.
  • this document features methods for treating cSCC where the methods can include, or consist essentially of, subjecting a mammal identified as having a sample including (a) or (b) to a surgery to remove the cSCC in the absence of an adjuvant therapy, where the (a) including the presence of at least one of (a-1) an altered level of an ACSL1 polypeptide or mRNA encoding an ACSL1 polypeptide, (a-2) an altered level of an ALDH1A1 polypeptide or mRNA encoding an ALDH1A1 polypeptide, (a-3) an altered level of an ALDH3A2 polypeptide or mRNA encoding an ALDH3A2 polypeptide, (a-4) an altered level of an ALOX12 polypeptide or mRNA encoding an ALOX12 polypeptide, (a-5) an altered level of a CALCOCO1 polypeptide or mRNA encoding a CALCOCO1 polypeptide, (a-6) an altered level of
  • the mammal can be a human.
  • the sample can be a tissue sample including a cSCC cell.
  • the adjuvant therapy can include radiation therapy.
  • the adjuvant therapy can include administering an anti-cancer drug to the mammal.
  • the anti-cancer drug can be cemiplimab-rwlc, nivolumab, ipilimumab, pembrolizumab, talimogene laherparepvec, cetuximab, capecitabine, carboplatin, or 5-FU. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.
  • FIG. 7A-7B show ROC curves for the risk score of metastasis ( Figure 7A) and the risk score of local recurrence or metastasis ( Figure 7B).
  • Figures 8A-8D show overall survival KM curves based on analysis with KRT2 (Figure 8A), ALDH3A2 (Figure 8B), ALOX12 (Figure 8C), and DMD (Figure 8D).
  • Figures 9A-9D show overall survival KM curves based on analysis with CXCL8 (Figure 9A), CDCA5 ( Figure 9B), ZNF750 (Figure 9C), and PRC1 ( Figure 9D).
  • Figures 10A-10B show an overall survival KM curve based on analysis with KRT2, ALDH3A2, ALOX12, DMD, CXCL8, CDCA5, ZNF750, and PRC1 with different risk score groups depicted.
  • Figures 11A-11F show overall survival KM curves based on analysis with KRT2 (Figure 11A), CALCOCO1 (Figure 11B), ALOX12 (Figure 11C), ACSL1 (Figure 11D), CYP4F3 (Figure 11E), and CASP14 (Figure 11F).
  • Figures 12A-12B show overall survival KM curves based on analysis with CEP55 (Figure 12A) and CDCA5 ( Figure 13B).
  • Figures 13A-13B show an overall survival KM curve based on analysis with CEP55, CDCA5, KRT2, ALOX12, CYP4F3, CALCOCO1, ACSL1, and CASP14 with different risk score groups depicted.
  • Figure 14B shows an ROC curve for the risk score of metastasis.
  • Figures 15A-15E show overall survival KM curves based on analysis with ALDH1A1 (Figure 15A), DMD (Figure 15B), ALOX12 (Figure 15C), TSGA10 ( Figure 15D), and ALDH3A2 ( Figure 11E).
  • Figures 16A-16D show overall survival KM curves based on analysis with NQO1 (Figure 16A), ZNF750 (Figure 16B), CDC6 (Figure 16C), and CDCA5 ( Figure 16D).
  • Figures 17A-17B show an overall survival KM curve based on analysis with ALDH1A1, DMD, ALOX12, TSGA10, ALDH3A2, NQO1, ZNF750, CDC6, and CDCA5 with different risk score groups depicted.
  • a sample e.g., a tissue sample containing one or more cSCC cells
  • a mammal having a cSCC can be assessed for the molecular signature of the cSCC to determine whether or not the mammal is likely to experience prolonged survival from cSCC (e.g., prolonged survival from the time of cSCC diagnosis) and/or whether the cSCC is likely to metastasize.
  • the methods and materials provided herein also can include treating a mammal having a cSCC where one or more cancer treatments are selected based, at least in part, on whether the mammal is likely to experience prolonged survival from cSCC (e.g., prolonged survival from the time of cSCC diagnosis) and/or whether or not the cSCC is likely to metastasize.
  • a mammal having a cSCC can be assessed to determine whether the mammal is likely to experience prolonged survival from cSCC (e.g., prolonged survival from the time of cSCC diagnosis) and/or to determine whether or not the cSCC is likely to metastasize (e.g., likely to metastasize to one or more lymph nodes) by detecting the Attorney Docket No.07039-2153WO1 / 2022-168 molecular signature of the cSCC.
  • a sample e.g., a tissue sample containing one or more cSCC cells
  • a mammal having a cSCC can be assessed to determine if the mammal is likely to experience prolonged survival from cSCC and/or whether the cSCC is likely to metastasize (e.g., likely to metastasize to one or more lymph nodes) based, at least in part, on the molecular signature of the cSCC.
  • a sample e.g., a tissue sample containing one or more cSCC cells obtained from a mammal having a cSCC can be assessed for the presence or absence of an altered level of a BIRC5 polypeptide (or mRNA encoding a BIRC5 polypeptide), an altered level of a MELK polypeptide (or mRNA encoding a MELK polypeptide), an altered level of an IFNE polypeptide (or mRNA encoding an IFNE polypeptide), an altered level of a HMGCS1 polypeptide (or mRNA encoding a HMGCS1 polypeptide), an altered level of an ANK2 polypeptide (or mRNA encoding an ANK2 polypeptide), an altered level of a LAMA2 polypeptide (or mRNA encoding a LAMA2 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide (or
  • a sample e.g., a tissue sample containing one or more cSCC cells obtained from a mammal having a cSCC can be assessed for the presence or absence of an altered level of a CSAG1 polypeptide (or mRNA encoding a CSAG1 polypeptide), an altered level of an UBE2C polypeptide (or mRNA encoding an UBE2C polypeptide), an altered level of an ANKRD1 polypeptide (or mRNA encoding an ANKRD1 polypeptide), an altered level of a CSMD3 polypeptide (or mRNA encoding a CSMD3 polypeptide), an altered level of a TOP2A polypeptide (or mRNA encoding a TOP2A polypeptide), an altered level of a TPX2 polypeptide (or mRNA encoding a TPX2 polypeptide), an altered level of a KSR2 polypeptide (or mRNA encoding a KSR2 polypeptide
  • any appropriate mammal having a cSCC can be assessed and/or treated as described herein.
  • mammals that can have cSCC and can be assessed and/or treated as described herein include, without limitation, humans, non-human primates (e.g., monkeys), dogs, cats, horses, cows, pigs, sheep, mice, and rats.
  • a human having a cSCC can be assessed and/or treated as described herein.
  • the cSCC can be any type of cSCC.
  • a cSCC to be assessed and/or treated as described herein can be any stage of cSCC (e.g., stage 0, stage I, stage II, stage III, or stage IV).
  • a cSCC to be assessed and/or treated as described herein can be at any location of a mammal (e.g., a human) being assessed and/or treated as described herein.
  • a cSCC can be at a location on a mammal’s body that has been exposed to ultraviolet (UV) radiation.
  • UV radiation ultraviolet
  • a cSCC can be at a location on a mammal’s body that has had exposure to the sun.
  • a cSCC can be at a location on a mammal’s body that has had exposure to a tanning lamp and/or a tanning bed.
  • locations on a mammal’s body where a cSCC that can be assessed and/or treated as described herein can occur include, without limitation, chest, back, legs, arms, face, soles of the feet, hands (e.g., palms of the hands), fingernail beds, toe nail beds, head, scalp, face (e.g., lips), periocular and eyelid, ears, neck, abdomen, finger nail matrix, and/or toe nail matrix.
  • the methods described herein can include identifying a mammal (e.g., a human) as having cSCC.
  • Any appropriate method can be used to identify a mammal as having cSCC. For example, physical examination (e.g., to examine the skin to look for signs that may indicate cSCC), imaging techniques (e.g., X-rays, computerized tomography (CT) scanning, and positron emission tomography (PET)), and/or laboratory examination (e.g., of a skin sample obtained by biopsy) can be used to identify a mammal (e.g., a human) as having cSCC.
  • CT computerized tomography
  • PET positron emission tomography
  • laboratory examination e.g., of a skin sample obtained by biopsy
  • a mammal can be identified as having a cSCC without having been subjected to a SLNb. In some cases, a mammal can be identified as having a cSCC and as having a negative SLNb.
  • a molecular signature used to determine whether or not mammal having a cSCC is likely to experience prolonged survival from cSCC e.g., prolonged survival from the time of cSCC diagnosis
  • the cSCC is likely to metastasize (e.g., likely to metastasize to one or more lymph nodes)
  • an altered level e.g., an increased level or a decreased level
  • polypeptides or mRNA encoding such polypeptides
  • a sample e.g., a tissue sample containing one or more cSCC cells
  • a mammal having a cSCC can be assessed for the presence or absence of an altered level (e.g., an increased level or a decreased level) of one or more polypeptides (or mRNA encoding such polypeptides) to determine whether or not the mammal is likely to experience prolonged survival from cSCC.
  • an altered level e.g., an increased level or a decreased level
  • a mammal having a cSCC can be identified as likely to experience prolonged survival from cSCC based, at least in part, on a molecular signature that includes the presence of an altered level of one or more polypeptides (or mRNA encoding such polypeptides) in a sample (e.g., a tissue sample containing one or more cSCC cells) obtained from the mammal.
  • a molecular signature that includes the presence of an altered level of one or more polypeptides (or mRNA encoding such polypeptides) in a sample (e.g., a tissue sample containing one or more cSCC cells) obtained from the mammal.
  • a sample e.g., a tissue sample containing one or more cSCC cells
  • a mammal having a cSCC can be assessed for the presence or absence of an altered level (e.g., an increased level or a decreased level) of one or more polypeptides (or mRNA encoding such polypeptides) to determine whether or not the cSCC is likely to metastasize (e.g., likely to metastasize to one or more lymph nodes).
  • an altered level e.g., an increased level or a decreased level
  • polypeptides or mRNA encoding such polypeptides
  • a cSCC can be identified as likely to metastasize (e.g., likely to metastasize to one or more lymph nodes) based, at least in part, on a molecular signature that includes the presence of an altered level of one or more polypeptides (or mRNA encoding such Attorney Docket No.07039-2153WO1 / 2022-168 polypeptides) in a sample (e.g., a tissue sample containing one or more cSCC cells) obtained from a mammal having the cSCC.
  • a sample e.g., a tissue sample containing one or more cSCC cells
  • an altered level can be an increased level of one or more polypeptides (or mRNA encoding such polypeptides) in a sample (e.g., a tissue sample containing one or more cSCC cells) obtained from a mammal having cSCC.
  • a sample e.g., a tissue sample containing one or more cSCC cells
  • the term “increased level” as used herein with respect to a level of a polypeptide (or mRNA encoding that polypeptide) in a sample refers to any level that is higher than a reference level of the polypeptide (or mRNA).
  • an altered level can be a decreased level of a polypeptide (or mRNA encoding that polypeptide) in a sample (e.g., a tissue sample containing one or more cSCC cells) obtained from a mammal having cSCC.
  • a sample e.g., a tissue sample containing one or more cSCC cells
  • the term “decreased level” as used herein with respect to a level of a polypeptide (or mRNA encoding that polypeptide) in a sample refers to any level that is lower than a reference level of the polypeptide (or mRNA).
  • reference level as used herein with respect to a level of a polypeptide (or mRNA) refers to the level of the polypeptide (or mRNA) typically observed in a control sample.
  • control samples are samples obtained from mammals that do not have cSCC (e.g., healthy mammals) and samples obtained from mammals having a cSCC at the time of initial diagnosis, where the mammal after treatment experienced metastases-free survival for at least 2 years.
  • an altered level e.g., an increased level or a decreased level
  • a polypeptide (or mRNA encoding a polypeptide) can be a level that is at least 1-fold different from a reference level of that polypeptide.
  • an increased level of a polypeptide (or mRNA encoding a polypeptide) can be a level that is at least 1-fold greater than a reference level of that polypeptide.
  • a decreased level of a polypeptide can be a level that is at least 1-fold less than a reference level of that polypeptide.
  • levels of polypeptides (or mRNAs) from comparable samples are used when determining whether or not a particular level is an altered level of a polypeptide (or mRNA).
  • a reference level can be the level of that polypeptide expressed in human cSCC cells obtained from a human at the time of initial diagnosis where that human after treatment experienced metastases-free survival of cSCC for at least 2 years.
  • a sample e.g., a tissue sample containing one or more cSCC cells obtained from a mammal (e.g., a human) having a cSCC can be assessed for the presence, absence, or level of any appropriate polypeptides (or mRNAs encoding the polypeptides).
  • polypeptides that can be present at an altered level in a sample (e.g., a tissue sample containing one or more cSCC cells) obtained from a mammal having a cSCC and likely to experience prolonged survival from cSCC (e.g., prolonged survival from the time of cSCC diagnosis) include, without limitation, CSAG1 polypeptides, UBE2C polypeptides, ANKRD1 polypeptides, CSMD3 polypeptides, TOP2A polypeptides, TPX2 polypeptides, KSR2 polypeptides, CSMD2 polypeptides, MMP20 polypeptides, PCSK1 polypeptides, TMEM150B polypeptides, ACSL1 polypeptides, TSGA10 polypeptides, KIT polypeptides, RGL3 polypeptides, PLA2G6 polypeptides, BIRC5 polypeptides, MELK polypeptides, IFNE polypeptides, HMGCS1 polypeptide
  • mRNAs that can be present at an altered level in a sample (e.g., a tissue sample containing one or more cSCC cells) obtained from a mammal having a cSCC and likely to experience prolonged survival (e.g., prolonged survival from the time of cSCC diagnosis) from cSCC include, without limitation, mRNAs encoding a CSAG1 polypeptide, mRNAs encoding an UBE2C polypeptide, mRNAs encoding a ANKRD1 polypeptide, mRNAs encoding a CSMD3 polypeptide, mRNAs encoding a TOP2A polypeptide, mRNAs encoding a TPX2 polypeptide, mRNAs encoding a KSR2 polypeptide, mRNAs encoding a CSMD2 polypeptide, mRNAs encoding a MMP20 polypeptide, mRNAs encoding a PCSK1 polypeptide, mRNAs
  • a sample obtained from a mammal having a cSCC can be assessed for the presence, absence, or level of a BIRC5 polypeptide (or mRNA encoding a BIRC5 polypeptide), a MELK polypeptide (or mRNA encoding a MELK polypeptide), an IFNE polypeptide (or mRNA encoding an IFNE polypeptide), a HMGCS1 polypeptide (or mRNA encoding a HMGCS1 polypeptide), an ANK2 polypeptide (or mRNA encoding an ANK2 polypeptide), a LAMA2 polypeptide (or mRNA encoding a LAMA2 polypeptide), a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), a FAM13C polypeptide (or mRNA encoding a FAM13C polypeptide (or mRNA encoding a FAM13C polypeptide (or
  • a sample obtained from a mammal having a cSCC can be assessed for the presence, absence, or level of a CSAG1 polypeptide (or mRNA encoding a CSAG1 polypeptide), an UBE2C polypeptide (or mRNA encoding an UBE2C polypeptide), an ANKRD1 polypeptide (or mRNA encoding an ANKRD1 polypeptide), a CSMD3 polypeptide (or mRNA encoding a CSMD3 polypeptide), a TOP2A polypeptide (or mRNA encoding a TOP2A polypeptide), a TPX2 polypeptide (or mRNA encoding a TPX2 polypeptide), a KSR2 polypeptide (or mRNA encoding a KSR2 polypeptide),
  • a sample obtained from a mammal having a cSCC can be assessed for the presence, absence, or level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide), a CDCA5 polypeptide (or mRNA encoding a CDCA5 polypeptide), a CXCL8 polypeptide (or mRNA encoding a CXCL8 polypeptide), a PRC1 polypeptide (or mRNA encoding a PRC1 polypeptide), a KRT2 polypeptide (or mRNA encoding a KRT2 polypeptide), an ALOX12 polypeptide (or mRNA encoding an ALOX12 polypeptide), an ALDH3A2 polypeptide (or mRNA encoding an ALDH3A2 polypeptide), a DMD polypeptide (or mRNA encoding a DMD polypeptide (or mRNA encoding a DMD polypeptide), a ZNF750 polypeptide
  • a sample e.g., a tissue sample containing one or more cSCC cells obtained from a mammal having a cSCC can be assessed Attorney Docket No.07039-2153WO1 / 2022-168 for the presence, absence, or level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), a FN1 polypeptide (or mRNA encoding a FN1 polypeptide), a MGAM polypeptide (or mRNA encoding a MGAM polypeptide), an EVPL polypeptide (or mRNA encoding an EVPL polypeptide), an AOX1 polypeptide (or mRNA encoding an AOX1 polypeptide), a PLA
  • a sample e.g., a tissue sample containing one or more cSCC cells obtained from a mammal (e.g., a human) having a cSCC is not assessed for the presence, absence, or level of a TP53 polypeptide (and an mRNA encoding a TP53 polypeptide), a CDKN2A polypeptide (and an mRNA encoding a CDKN2A polypeptide), a NOTCH1 polypeptide (and an mRNA encoding a NOTCH1 polypeptide), a FAT1 polypeptide (and an mRNA encoding a FAT1 polypeptide), a HRAS polypeptide (and an mRNA encoding a HRAS polypeptide), and/or a INPP5A polypeptide (and an mRNA encoding a INPP5A polypeptide).
  • a sample e.g., a tissue sample containing one or more cSCC cells obtained from a mammal (e.g., a human) having a cSCC is not assessed for the presence, absence, or level of a polypeptide (or an mRNA encoding a polypeptide) described in Wysong et al. (J. Am. Acad. Dermatol., 84(2):361-369 (2021)).
  • an altered level of a polypeptide can be an altered level (e.g., an increased level increased level or a decreased level) of a CSAG1 polypeptide (or an altered level of an mRNA encoding a CSAG1 polypeptide).
  • An example of a CSAG1 polypeptide is, without limitation, the polypeptide set forth in the National Center for Attorney Docket No.07039-2153WO1 / 2022-168 Biotechnology Information (NCBI) databases at, for example, accession no. NP_001096046 (version NP_001096046.2).
  • an altered level of a CSAG1 polypeptide can be any level that is at least 1-fold different than a reference level of the CSAG1 polypeptide (or a reference level of an mRNA encoding a CSAG1 polypeptide).
  • a reference level of an mRNA encoding a CSAG1 polypeptide in humans can be a level of such mRNA that is about 0.014 fragment per kilobase per million (FPKM) as measured in a RNA-seq technology platform.
  • an increased level of an mRNA encoding a CSAG1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a CSAG1 polypeptide.
  • a decreased level of an mRNA encoding a CSAG1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a CSAG1 polypeptide.
  • an altered level of a polypeptide can be an altered level (e.g., an increased level increased level or a decreased level) of an UBE2C polypeptide (or an altered level of an mRNA encoding an UBE2C polypeptide).
  • An example of an UBE2C polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_008950 (version NP_008950.1).
  • an altered level of an UBE2C polypeptide can be any level that is at least 1-fold different than a reference level of the UBE2C polypeptide (or a reference level of an mRNA encoding an UBE2C polypeptide).
  • a reference level of an mRNA encoding an UBE2C polypeptide in humans can be a level of such mRNA that is about 3.234 FPKM as measured in a RNA-seq technology platform.
  • an increased level of an mRNA encoding an UBE2C polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding an UBE2C polypeptide.
  • a decreased level of an mRNA encoding an UBE2C polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at Attorney Docket No.07039-2153WO1 / 2022-168 least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding an UBE2C polypeptide.
  • an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of an ANKRD1 polypeptide (or an altered level of an mRNA encoding an ANKRD1 polypeptide).
  • an ANKRD1 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_055206 (version NP_055206.2).
  • an altered level of an ANKRD1 polypeptide can be any level that is at least 1-fold different than a reference level of the ANKRD1 polypeptide (or a reference level of an mRNA encoding an ANKRD1 polypeptide).
  • a reference level of an mRNA encoding an ANKRD1 polypeptide in humans can be a level of such mRNA that is about 0.258 FPKM as measured in a RNA-seq technology platform.
  • an increased level of an mRNA encoding an ANKRD1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding an ANKRD1 polypeptide.
  • a decreased level of an mRNA encoding an ANKRD1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding an ANKRD1 polypeptide.
  • an altered level of a polypeptide can be an altered level (e.g., an increased level increased level or a decreased level) of a CSMD3 polypeptide (or an altered level of an mRNA encoding a CSMD3 polypeptide).
  • An example of a CSMD3 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_937756 (version NP_937756.1).
  • an altered level of a CSMD3 polypeptide can be any level that is at least 1-fold different than a reference level of the CSMD3 polypeptide (or a reference level of an mRNA encoding a CSMD3 polypeptide).
  • a reference level of an mRNA encoding a CSMD3 polypeptide in humans can be a level of such mRNA that is about 0.026 FPKM as measured in a RNA-seq technology platform.
  • an increased level of an mRNA encoding a CSMD3 polypeptide can be a level that is at least 1 (e.g., at Attorney Docket No.07039-2153WO1 / 2022-168 least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a CSMD3 polypeptide.
  • a decreased level of an mRNA encoding a CSMD3 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a CSMD3 polypeptide.
  • an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a TOP2A polypeptide (or an altered level of an mRNA encoding a TOP2A polypeptide).
  • an altered level of a TOP2A polypeptide can be any level that is at least 1-fold different than a reference level of the TOP2A polypeptide (or a reference level of an mRNA encoding a TOP2A polypeptide).
  • a reference level of an mRNA encoding a TOP2A polypeptide in humans can be a level of such mRNA that is about 13.6 FPKM as measured in a RNA-seq technology platform.
  • an increased level of an mRNA encoding a TOP2A polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a TOP2A polypeptide.
  • a decreased level of an mRNA encoding a TOP2A polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a TOP2A polypeptide.
  • an altered level of a polypeptide can be an altered level (e.g., an increased level increased level or a decreased level) of a TPX2 polypeptide (or an altered level of an mRNA encoding a TPX2 polypeptide).
  • An example of a TPX2 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_036244 (version NP_036244.2).
  • an altered level of a TPX2 polypeptide can be any level that is at least 1-fold different than a reference level of the TPX2 polypeptide (or a reference level of an mRNA encoding a TPX2 polypeptide).
  • a reference level of an mRNA Attorney Docket No.07039-2153WO1 / 2022-168 encoding a TPX2 polypeptide in humans can be a level of such mRNA that is about 5.956 FPKM as measured in a RNA-seq technology platform.
  • an increased level of an mRNA encoding a TPX2 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a TPX2 polypeptide.
  • a decreased level of an mRNA encoding a TPX2 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a TPX2 polypeptide.
  • an altered level of a polypeptide can be an altered level (e.g., an increased level increased level or a decreased level) of a KSR2 polypeptide (or an altered level of an mRNA encoding a KSR2 polypeptide).
  • An example of a KSR2 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_775869 (version NP_775869.4).
  • an altered level of a KSR2 polypeptide can be any level that is at least 1-fold different than a reference level of the KSR2 polypeptide (or a reference level of an mRNA encoding a KSR2 polypeptide).
  • a reference level of an mRNA encoding a KSR2 polypeptide in humans can be a level of such mRNA that is about 0.022 FPKM as measured in a RNA-seq technology platform.
  • an increased level of an mRNA encoding a KSR2 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a KSR2 polypeptide.
  • a decreased level of an mRNA encoding a KSR2 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a KSR2 polypeptide.
  • an altered level of a polypeptide can be an altered level (e.g., an increased level increased level or a decreased level) of a CSMD2 polypeptide (or an altered level of an mRNA encoding a CSMD2 polypeptide).
  • An example of a CSMD2 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_001268885 (version NP_001268885.1).
  • an altered level of a CSMD2 polypeptide can be any Attorney Docket No.07039-2153WO1 / 2022-168 level that is at least 1-fold different than a reference level of the CSMD2 polypeptide (or a reference level of an mRNA encoding a CSMD2 polypeptide).
  • a reference level of an mRNA encoding a CSMD2 polypeptide in humans can be a level of such mRNA that is about 0.347 FPKM as measured in a RNA-seq technology platform.
  • an increased level of an mRNA encoding a CSMD2 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a CSMD2 polypeptide.
  • a decreased level of an mRNA encoding a CSMD2 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a CSMD2 polypeptide.
  • an altered level of a polypeptide can be an altered level (e.g., an increased level increased level or a decreased level) of a MMP20 polypeptide (or an altered level of an mRNA encoding a MMP20 polypeptide).
  • An example of a MMP20 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_004762 (version NP_004762.2).
  • an altered level of a MMP20 polypeptide can be any level that is at least 1-fold different than a reference level of the MMP20 polypeptide (or a reference level of an mRNA encoding a MMP20 polypeptide).
  • a reference level of an mRNA encoding a MMP20 polypeptide in humans can be a level of such mRNA that is about 0.001 FPKM as measured in a RNA-seq technology platform.
  • an increased level of an mRNA encoding a MMP20 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a MMP20 polypeptide.
  • a decreased level of an mRNA encoding a MMP20 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a MMP20 polypeptide.
  • an altered level of a polypeptide can be an altered level (e.g., an increased level increased level or a decreased level) of a PCSK1 polypeptide (or an Attorney Docket No.07039-2153WO1 / 2022-168 altered level of an mRNA encoding a PCSK1 polypeptide).
  • An example of a PCSK1 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_001171346 (version NP_001171346.1).
  • an altered level of a PCSK1 polypeptide can be any level that is at least 1-fold different than a reference level of the PCSK1 polypeptide (or a reference level of an mRNA encoding a PCSK1 polypeptide).
  • a reference level of an mRNA encoding a PCSK1 polypeptide in humans can be a level of such mRNA that is about 0.341 FPKM as measured in a RNA-seq technology platform.
  • an increased level of an mRNA encoding a PCSK1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a PCSK1 polypeptide.
  • a decreased level of an mRNA encoding a PCSK1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a PCSK1 polypeptide.
  • an altered level of a polypeptide can be an altered level (e.g., an increased level increased level or a decreased level) of a TMEM150B polypeptide (or an altered level of an mRNA encoding a TMEM150B polypeptide).
  • An example of a TMEM150B polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_001078957 (version NP_001078957.1).
  • an altered level of a TMEM150B polypeptide can be any level that is at least 1-fold different than a reference level of the TMEM150B polypeptide (or a reference level of an mRNA encoding a TMEM150B polypeptide).
  • a reference level of an mRNA encoding a TMEM150B polypeptide in humans can be a level of such mRNA that is about 0.018 FPKM as measured in a RNA-seq technology platform.
  • an increased level of an mRNA encoding a TMEM150B polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a TMEM150B polypeptide.
  • a decreased level of an mRNA encoding a TMEM150B polypeptide can be a level Attorney Docket No.07039-2153WO1 / 2022-168 that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a TMEM150B polypeptide.
  • an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of an ACSL1 polypeptide (or an altered level of an mRNA encoding an ACSL1 polypeptide).
  • an ACSL1 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_001986 (version NP_001986.2).
  • an altered level of an ACSL1 polypeptide can be any level that is at least 1-fold different than a reference level of the ACSL1 polypeptide (or a reference level of an mRNA encoding an ACSL1 polypeptide).
  • a reference level of an mRNA encoding an ACSL1 polypeptide in humans can be a level of such mRNA that is about 42.066 FPKM as measured in a RNA-seq technology platform.
  • an increased level of an mRNA encoding an ACSL1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding an ACSL1 polypeptide.
  • a decreased level of an mRNA encoding an ACSL1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding an ACSL1 polypeptide.
  • an altered level of a polypeptide can be an altered level (e.g., an increased level increased level or a decreased level) of a TSGA10 polypeptide (or an altered level of an mRNA encoding a TSGA10 polypeptide).
  • An example of a TSGA10 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_079520 (version NP_079520.1).
  • an altered level of a TSGA10 polypeptide can be any level that is at least 1-fold different than a reference level of the TSGA10 polypeptide (or a reference level of an mRNA encoding a TSGA10 polypeptide).
  • a reference level of an mRNA encoding a TSGA10 polypeptide in humans can be a level of such mRNA that is about 1.308 FPKM as measured in a RNA-seq technology platform.
  • an Attorney Docket No.07039-2153WO1 / 2022-168 increased level of an mRNA encoding a TSGA10 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a TSGA10 polypeptide.
  • a decreased level of an mRNA encoding a TSGA10 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a TSGA10 polypeptide.
  • an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a KIT polypeptide (or an altered level of an mRNA encoding a KIT polypeptide).
  • KIT polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_000213 (version NP_000213.1).
  • an altered level of a KIT polypeptide can be any level that is at least 1-fold different than a reference level of the KIT polypeptide (or a reference level of an mRNA encoding a KIT polypeptide).
  • a reference level of an mRNA encoding a KIT polypeptide in humans can be a level of such mRNA that is about 8.414 FPKM as measured in a RNA- seq technology platform.
  • an increased level of an mRNA encoding a KIT polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a KIT polypeptide.
  • a decreased level of an mRNA encoding a KIT polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a KIT polypeptide.
  • an altered level of a polypeptide can be an altered level (e.g., an increased level increased level or a decreased level) of a RGL3 polypeptide (or an altered level of an mRNA encoding a RGL3 polypeptide).
  • An example of a RGL3 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_001155088 (version NP_001155088.2).
  • an altered level of a RGL3 polypeptide can be any level that is at least 1-fold different than a reference level of the RGL3 polypeptide (or a reference Attorney Docket No.07039-2153WO1 / 2022-168 level of an mRNA encoding a RGL3 polypeptide).
  • a reference level of an mRNA encoding a RGL3 polypeptide in humans can be a level of such mRNA that is about 0.224 FPKM as measured in a RNA-seq technology platform.
  • an increased level of an mRNA encoding a RGL3 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a RGL3 polypeptide.
  • a decreased level of an mRNA encoding a RGL3 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a RGL3 polypeptide.
  • an altered level of a polypeptide can be an altered level (e.g., an increased level increased level or a decreased level) of a PLA2G6 polypeptide (or an altered level of an mRNA encoding a PLA2G6 polypeptide).
  • An example of a PLA2G6 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_003551 (version NP_003551.2).
  • an altered level of a PLA2G6 polypeptide can be any level that is at least 1-fold different than a reference level of the PLA2G6 polypeptide (or a reference level of an mRNA encoding a PLA2G6 polypeptide).
  • a reference level of an mRNA encoding a PLA2G6 polypeptide in humans can be a level of such mRNA that is about 3.763 FPKM as measured in a RNA-seq technology platform.
  • an increased level of an mRNA encoding a PLA2G6 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a PLA2G6 polypeptide.
  • a decreased level of an mRNA encoding a PLA2G6 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a PLA2G6 polypeptide.
  • an altered level of a polypeptide can be an altered level (e.g., an increased level increased level or a decreased level) of a BIRC5 polypeptide (or an altered level of an mRNA encoding a BIRC5 polypeptide).
  • An example of a BIRC5 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for Attorney Docket No.07039-2153WO1 / 2022-168 example, accession no. NP_001159 (version NP_001159.2).
  • an altered level of a BIRC5 polypeptide can be any level that is at least 1-fold different than a reference level of the BIRC5 polypeptide (or a reference level of an mRNA encoding a BIRC5 polypeptide).
  • a reference level of an mRNA encoding a BIRC5 polypeptide in humans can be a level of such mRNA that is about 0.650 FPKM as measured in a RNA-seq technology platform.
  • an increased level of an mRNA encoding a BIRC5 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a BIRC5 polypeptide.
  • a decreased level of an mRNA encoding a BIRC5 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a BIRC5 polypeptide.
  • an altered level of a polypeptide can be an altered level (e.g., an increased level increased level or a decreased level) of a MELK polypeptide (or an altered level of an mRNA encoding a MELK polypeptide).
  • An example of a MELK polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_055606 (version NP_055606.1).
  • an altered level of a MELK polypeptide can be any level that is at least 1-fold different than a reference level of the MELK polypeptide (or a reference level of an mRNA encoding a MELK polypeptide).
  • a reference level of an mRNA encoding a MELK polypeptide in humans can be a level of such mRNA that is about 3.543 FPKM as measured in a RNA-seq technology platform.
  • an increased level of an mRNA encoding a MELK polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a MELK polypeptide.
  • a decreased level of an mRNA encoding a MELK polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a MELK polypeptide.
  • an altered level of a polypeptide can be an altered level (e.g., an increased level increased level or a decreased level) of an IFNE polypeptide (or an Attorney Docket No.07039-2153WO1 / 2022-168 altered level of an mRNA encoding an IFNE polypeptide).
  • An example of an IFNE polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NM_176891 (version NM_176891.5).
  • an altered level of an IFNE polypeptide can be any level that is at least 1-fold different than a reference level of the IFNE polypeptide (or a reference level of an mRNA encoding an IFNE polypeptide).
  • a reference level of an mRNA encoding an IFNE polypeptide in humans can be a level of such mRNA that is about 0.578 FPKM as measured in a RNA-seq technology platform.
  • an increased level of an mRNA encoding an IFNE polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding an IFNE polypeptide.
  • a decreased level of an mRNA encoding an IFNE polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding an IFNE polypeptide.
  • an altered level of a polypeptide can be an altered level (e.g., an increased level increased level or a decreased level) of a HMGCS1 polypeptide (or an altered level of an mRNA encoding a HMGCS1 polypeptide).
  • An example of a HMGCS1 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_001351117 (version NP_001351117.1).
  • an altered level of a HMGCS1 polypeptide can be any level that is at least 1-fold different than a reference level of the HMGCS1 polypeptide (or a reference level of an mRNA encoding a HMGCS1 polypeptide).
  • a reference level of an mRNA encoding a HMGCS1 polypeptide in humans can be a level of such mRNA that is about 34.706 FPKM as measured in a RNA-seq technology platform.
  • an increased level of an mRNA encoding a HMGCS1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a HMGCS1 polypeptide.
  • a decreased level of an mRNA encoding a HMGCS1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, Attorney Docket No.07039-2153WO1 / 2022-168 at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a HMGCS1 polypeptide.
  • an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of an ANK2 polypeptide (or an altered level of an mRNA encoding an ANK2 polypeptide).
  • an ANK2 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_001139 (version NP_001139.3).
  • an altered level of an ANK2 polypeptide can be any level that is at least 1-fold different than a reference level of the ANK2 polypeptide (or a reference level of an mRNA encoding an ANK2 polypeptide).
  • a reference level of an mRNA encoding an ANK2 polypeptide in humans can be a level of such mRNA that is about 12.926 FPKM as measured in a RNA-seq technology platform.
  • an increased level of an mRNA encoding an ANK2 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding an ANK2 polypeptide.
  • a decreased level of an mRNA encoding an ANK2 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding an ANK2 polypeptide.
  • an altered level of a polypeptide can be an altered level (e.g., an increased level increased level or a decreased level) of a LAMA2 polypeptide (or an altered level of an mRNA encoding a LAMA2 polypeptide).
  • An example of a LAMA2 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_000417 (version NP_000417.3).
  • an altered level of a LAMA2 polypeptide can be any level that is at least 1-fold different than a reference level of the LAMA2 polypeptide (or a reference level of an mRNA encoding a LAMA2 polypeptide).
  • a reference level of an mRNA encoding a LAMA2 polypeptide in humans can be a level of such mRNA that is about 40.295 FPKM as measured in a RNA-seq technology platform.
  • an increased level of an mRNA encoding a LAMA2 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least Attorney Docket No.07039-2153WO1 / 2022-168 35, or at least 50) fold greater than a reference level of mRNA encoding a LAMA2 polypeptide.
  • a decreased level of an mRNA encoding a LAMA2 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a LAMA2 polypeptide.
  • an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a CYP2U1 polypeptide (or an altered level of an mRNA encoding a CYP2U1 polypeptide).
  • a CYP2U1 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_898898 (version NP_898898.1).
  • an altered level of a CYP2U1 polypeptide can be any level that is at least 1-fold different than a reference level of the CYP2U1 polypeptide (or a reference level of an mRNA encoding a CYP2U1 polypeptide).
  • a reference level of an mRNA encoding a CYP2U1 polypeptide in humans can be a level of such mRNA that is about 0.465 FPKM as measured in a RNA-seq technology platform.
  • an increased level of an mRNA encoding a CYP2U1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a CYP2U1 polypeptide.
  • a decreased level of an mRNA encoding a CYP2U1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a CYP2U1 polypeptide.
  • an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a FAM13C polypeptide (or an altered level of an mRNA encoding a FAM13C polypeptide).
  • FAM13C polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_937858 (version NP_937858.2).
  • an altered level of a FAM13C polypeptide can be any level that is at least 1-fold different than a reference level of the FAM13C polypeptide (or a reference level of an mRNA encoding a FAM13C polypeptide).
  • a reference Attorney Docket No.07039-2153WO1 / 2022-168 level of an mRNA encoding a FAM13C polypeptide in humans can be a level of such mRNA that is about 3.148 FPKM as measured in a RNA-seq technology platform.
  • an increased level of an mRNA encoding a FAM13C polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a FAM13C polypeptide.
  • a decreased level of an mRNA encoding a FAM13C polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a FAM13C polypeptide.
  • an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a COL25A1 polypeptide (or an altered level of an mRNA encoding a COL25A1 polypeptide).
  • an example of a COL25A1 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_942014 (version NP_942014.1).
  • an altered level of a COL25A1 polypeptide can be any level that is at least 1-fold different than a reference level of the COL25A1 polypeptide (or a reference level of an mRNA encoding a COL25A1 polypeptide).
  • a reference level of an mRNA encoding a COL25A1 polypeptide in humans can be a level of such mRNA that is about 0.294 FPKM as measured in a RNA-seq technology platform.
  • an increased level of an mRNA encoding a COL25A1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a COL25A1 polypeptide.
  • a decreased level of an mRNA encoding a COL25A1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a COL25A1 polypeptide.
  • an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a TG polypeptide (or an altered level of an mRNA encoding a TG polypeptide).
  • a TG polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession Attorney Docket No.07039-2153WO1 / 2022-168 no. XP_006716685 (version XP_006716685.1).
  • an altered level of a TG polypeptide can be any level that is at least 1-fold different than a reference level of the TG polypeptide (or a reference level of an mRNA encoding a TG polypeptide).
  • a reference level of an mRNA encoding a TG polypeptide in humans can be a level of such mRNA that is about 3.017 FPKM as measured in a RNA-seq technology platform.
  • an increased level of an mRNA encoding a TG polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a TG polypeptide.
  • a decreased level of an mRNA encoding a TG polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a TG polypeptide.
  • an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a FAT4 polypeptide (or an altered level of an mRNA encoding a FAT4 polypeptide).
  • FAT4 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. XP_047272107 (version XP_047272107.1).
  • an altered level of a FAT4 polypeptide can be any level that is at least 1-fold different than a reference level of the FAT4 polypeptide (or a reference level of an mRNA encoding a FAT4 polypeptide).
  • a reference level of an mRNA encoding a FAT4 polypeptide in humans can be a level of such mRNA that is about 6.658 FPKM as measured in a RNA-seq technology platform.
  • an increased level of an mRNA encoding a FAT4 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a FAT4 polypeptide.
  • a decreased level of an mRNA encoding a FAT4 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a FAT4 polypeptide.
  • an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of an AOX1 polypeptide (or an Attorney Docket No.07039-2153WO1 / 2022-168 altered level of an mRNA encoding an AOX1 polypeptide).
  • an AOX1 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, XP_011509364 (version XP_011509364.1).
  • an altered level of an AOX1 polypeptide can be any level that is at least 1-fold different than a reference level of the AOX1 polypeptide (or a reference level of an mRNA encoding an AOX1 polypeptide).
  • an increased level of an mRNA encoding an AOX1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding an AOX1 polypeptide.
  • a decreased level of an mRNA encoding an AOX1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding an AOX1 polypeptide.
  • an altered level of a polypeptide can be an altered level (e.g., an increased level increased level or a decreased level) of a CDC6 polypeptide (or an altered level of an mRNA encoding a CDC6 polypeptide).
  • An example of a CDC6 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, XP_011523844 (version XP_011523844.1).
  • an altered level of a CDC6 polypeptide can be any level that is at least 1-fold different than a reference level of the CDC6 polypeptide (or a reference level of an mRNA encoding a CDC6 polypeptide).
  • an increased level of an mRNA encoding a CDC6 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a CDC6 polypeptide.
  • a decreased level of an mRNA encoding a CDC6 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a CDC6 polypeptide.
  • an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a FN1 polypeptide (or an altered level of an mRNA encoding a FN1 polypeptide).
  • a FN1 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, Attorney Docket No.07039-2153WO1 / 2022-168 NP_001293058 (version NP_001293058.2).
  • an altered level of a FN1 polypeptide can be any level that is at least 1-fold different than a reference level of the FN1 polypeptide (or a reference level of an mRNA encoding a FN1 polypeptide).
  • an increased level of an mRNA encoding a FN1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a FN1 polypeptide.
  • a decreased level of an mRNA encoding a FN1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a FN1 polypeptide.
  • an altered level of a polypeptide can be an altered level (e.g., an increased level increased level or a decreased level) of a MGAM polypeptide (or an altered level of an mRNA encoding a MGAM polypeptide).
  • An example of a MGAM polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, XP_011514972 (version XP_011514972.1).
  • an altered level of a MGAM polypeptide can be any level that is at least 1-fold different than a reference level of the MGAM polypeptide (or a reference level of an mRNA encoding a MGAM polypeptide).
  • an increased level of an mRNA encoding a MGAM polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a MGAM polypeptide.
  • a decreased level of an mRNA encoding a MGAM polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a MGAM polypeptide.
  • an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a CYP2E1 polypeptide (or an altered level of an mRNA encoding a CYP2E1 polypeptide).
  • a CYP2E1 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, NP_000764 (version NP_000764.1).
  • an altered level of a CYP2E1 polypeptide can be any level that is at least Attorney Docket No.07039-2153WO1 / 2022-168 1-fold different than a reference level of the CYP2E1 polypeptide (or a reference level of an mRNA encoding a CYP2E1 polypeptide).
  • an increased level of an mRNA encoding a CYP2E1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a CYP2E1 polypeptide.
  • a decreased level of an mRNA encoding a CYP2E1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a CYP2E1 polypeptide.
  • an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a CYP4F3 polypeptide (or an altered level of an mRNA encoding a CYP4F3 polypeptide).
  • a CYP4F3 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, XP_011526316 (version XP_011526316.1).
  • an altered level of a CYP4F3 polypeptide can be any level that is at least 1-fold different than a reference level of the CYP4F3 polypeptide (or a reference level of an mRNA encoding a CYP4F3 polypeptide).
  • an increased level of an mRNA encoding a CYP4F3 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a CYP4F3 polypeptide.
  • a decreased level of an mRNA encoding a CYP4F3 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a CYP4F3 polypeptide.
  • an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a CALCOCO1 polypeptide (or an altered level of an mRNA encoding a CALCOCO1 polypeptide).
  • an example of a CALCOCO1 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, XP_011536903 (version XP_011536903.1).
  • an altered level of a CALCOCO1 polypeptide can be any level that is at least 1-fold different than a reference level of the CALCOCO1 polypeptide (or a reference level of an mRNA encoding a CALCOCO1 Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide).
  • an increased level of an mRNA encoding a CALCOCO1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a CALCOCO1 polypeptide.
  • a decreased level of an mRNA encoding a CALCOCO1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a CALCOCO1 polypeptide.
  • an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of an EVPL polypeptide (or an altered level of an mRNA encoding an EVPL polypeptide).
  • an EVPL polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, NP_001307676 (version NP_001307676.1).
  • an altered level of an EVPL polypeptide (or an mRNA encoding an EVPL polypeptide) can be any level that is at least 1-fold different than a reference level of the EVPL polypeptide (or a reference level of an mRNA encoding an EVPL polypeptide).
  • an increased level of an mRNA encoding an EVPL polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding an EVPL polypeptide.
  • a decreased level of an mRNA encoding an EVPL polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding an EVPL polypeptide.
  • an altered level of a polypeptide can be an altered level (e.g., an increased level increased level or a decreased level) of a FASN polypeptide (or an altered level of an mRNA encoding a FASN polypeptide).
  • An example of a FASN polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, XP_011521840 (version XP_011521840.1).
  • an altered level of a FASN polypeptide can be any level that is at least 1-fold different than a reference level of the FASN polypeptide (or a reference level of an mRNA encoding a FASN polypeptide).
  • an increased level of an mRNA encoding a FASN polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at Attorney Docket No.07039-2153WO1 / 2022-168 least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a FASN polypeptide.
  • a decreased level of an mRNA encoding a FASN polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a FASN polypeptide.
  • an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a CASP14 polypeptide (or an altered level of an mRNA encoding a CASP14 polypeptide).
  • CASP14 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, XP_011526163 (version XP_011526163.1).
  • an altered level of a CASP14 polypeptide can be any level that is at least 1-fold different than a reference level of the CASP14 polypeptide (or a reference level of an mRNA encoding a CASP14 polypeptide).
  • an increased level of an mRNA encoding a CASP14 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a CASP14 polypeptide.
  • a decreased level of an mRNA encoding a CASP14 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a CASP14 polypeptide.
  • an altered level of a polypeptide can be an altered level (e.g., an increased level increased level or a decreased level) of a ZNF750 polypeptide (or an altered level of an mRNA encoding a ZNF750 polypeptide).
  • An example of a ZNF750 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, NP_078978 (version NP_078978.2).
  • an altered level of a ZNF750 polypeptide can be any level that is at least 1- fold different than a reference level of the ZNF750 polypeptide (or a reference level of an mRNA encoding a ZNF750 polypeptide).
  • an increased level of an mRNA encoding a ZNF750 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a ZNF750 polypeptide.
  • a decreased Attorney Docket No.07039-2153WO1 / 2022-168 level of an mRNA encoding a ZNF750 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a ZNF750 polypeptide.
  • an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a TRPM1 polypeptide (or an altered level of an mRNA encoding a TRPM1 polypeptide).
  • TRPM1 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, XP_054187771 (version XP_054187771.1).
  • an altered level of a TRPM1 polypeptide can be any level that is at least 1-fold different than a reference level of the TRPM1 polypeptide (or a reference level of an mRNA encoding a TRPM1 polypeptide).
  • an increased level of an mRNA encoding a TRPM1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a TRPM1 polypeptide.
  • a decreased level of an mRNA encoding a TRPM1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a TRPM1 polypeptide.
  • an altered level of a polypeptide can be an altered level (e.g., an increased level increased level or a decreased level) of a CDCA5 polypeptide (or an altered level of an mRNA encoding a CDCA5 polypeptide).
  • An example of a CDCA5 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, XP_011543045 (version XP_011543045.1).
  • an altered level of a CDCA5 polypeptide can be any level that is at least 1-fold different than a reference level of the CDCA5 polypeptide (or a reference level of an mRNA encoding a CDCA5 polypeptide).
  • an increased level of an mRNA encoding a CDCA5 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a CDCA5 polypeptide.
  • a decreased level of an mRNA encoding a CDCA5 polypeptide can be a level that is at least 1 (e.g., at Attorney Docket No.07039-2153WO1 / 2022-168 least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a CDCA5 polypeptide.
  • an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a CXCL8 polypeptide (or an altered level of an mRNA encoding a CXCL8 polypeptide).
  • CXCL8 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, NP_000575 (version NP_000575.1).
  • an altered level of a CXCL8 polypeptide can be any level that is at least 1- fold different than a reference level of the CXCL8 polypeptide (or a reference level of an mRNA encoding a CXCL8 polypeptide).
  • an increased level of an mRNA encoding a CXCL8 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a CXCL8 polypeptide.
  • a decreased level of an mRNA encoding a CXCL8 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a CXCL8 polypeptide.
  • an altered level of a polypeptide can be an altered level (e.g., an increased level increased level or a decreased level) of a PRC1 polypeptide (or an altered level of an mRNA encoding a PRC1 polypeptide).
  • An example of a PRC1 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, XP_016878203 (version XP_016878203.1).
  • an altered level of a PRC1 polypeptide can be any level that is at least 1-fold different than a reference level of the PRC1 polypeptide (or a reference level of an mRNA encoding a PRC1 polypeptide).
  • an increased level of an mRNA encoding a PRC1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a PRC1 polypeptide.
  • a decreased level of an mRNA encoding a PRC1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a PRC1 polypeptide.
  • Attorney Docket No.07039-2153WO1 / 2022-168 an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a KRT2 polypeptide (or an altered level of an mRNA encoding a KRT2 polypeptide).
  • KRT2 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, NP_000414 (version NP_000414.2).
  • an altered level of a KRT2 polypeptide can be any level that is at least 1- fold different than a reference level of the KRT2 polypeptide (or a reference level of an mRNA encoding a KRT2 polypeptide).
  • an increased level of an mRNA encoding a KRT2 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a KRT2 polypeptide.
  • a decreased level of an mRNA encoding a KRT2 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a KRT2 polypeptide.
  • an altered level of a polypeptide can be an altered level (e.g., an increased level increased level or a decreased level) of an ALOX12 polypeptide (or an altered level of an mRNA encoding an ALOX12 polypeptide).
  • An example of an ALOX12 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, XP_011522082 (version XP_011522082.2).
  • an altered level of an ALOX12 polypeptide can be any level that is at least 1-fold different than a reference level of the ALOX12 polypeptide (or a reference level of an mRNA encoding an ALOX12 polypeptide).
  • an increased level of an mRNA encoding an ALOX12 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding an ALOX12 polypeptide.
  • a decreased level of an mRNA encoding an ALOX12 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding an ALOX12 polypeptide.
  • Attorney Docket No.07039-2153WO1 / 2022-168 an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of an ALDH3A2 polypeptide (or an altered level of an mRNA encoding an ALDH3A2 polypeptide).
  • an ALDH3A2 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, XP_024306419 (version XP_024306419.1).
  • an altered level of an ALDH3A2 polypeptide can be any level that is at least 1-fold different than a reference level of the ALDH3A2 polypeptide (or a reference level of an mRNA encoding an ALDH3A2 polypeptide).
  • an increased level of an mRNA encoding an ALDH3A2 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding an ALDH3A2 polypeptide.
  • a decreased level of an mRNA encoding an ALDH3A2 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding an ALDH3A2 polypeptide.
  • an altered level of a polypeptide can be an altered level (e.g., an increased level increased level or a decreased level) of a DMD polypeptide (or an altered level of an mRNA encoding a DMD polypeptide).
  • An example of a DMD polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, XP_006724532 (version XP_006724532.1).
  • an altered level of a DMD polypeptide can be any level that is at least 1-fold different than a reference level of the DMD polypeptide (or a reference level of an mRNA encoding a DMD polypeptide).
  • an increased level of an mRNA encoding a DMD polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a DMD polypeptide.
  • a decreased level of an mRNA encoding a DMD polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a DMD polypeptide.
  • Attorney Docket No.07039-2153WO1 / 2022-168 an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a CEP55 polypeptide (or an altered level of an mRNA encoding a CEP55 polypeptide).
  • CEP55 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, XP_016871862 (version XP_016871862.1).
  • an altered level of a CEP55 polypeptide can be any level that is at least 1-fold different than a reference level of the CEP55 polypeptide (or a reference level of an mRNA encoding a CEP55 polypeptide).
  • an increased level of an mRNA encoding a CEP55 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a CEP55 polypeptide.
  • a decreased level of an mRNA encoding a CEP55 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a CEP55 polypeptide.
  • an altered level of a polypeptide can be an altered level (e.g., an increased level increased level or a decreased level) of a CYP4F22 polypeptide (or an altered level of an mRNA encoding a CYP4F22 polypeptide).
  • An example of a CYP4F22 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, XP_011525994 (version XP_011525994.1).
  • an altered level of a CYP4F22 polypeptide can be any level that is at least 1-fold different than a reference level of the CYP4F22 polypeptide (or a reference level of an mRNA encoding a CYP4F22 polypeptide).
  • an increased level of an mRNA encoding a CYP4F22 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a CYP4F22 polypeptide.
  • a decreased level of an mRNA encoding a CYP4F22 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a CYP4F22 polypeptide.
  • an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a CERS3 polypeptide (or an altered level of an mRNA encoding a CERS3 polypeptide).
  • CERS3 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, XP_011519657 (version XP_011519657.1).
  • an altered level of a CERS3 polypeptide can be any level that is at least 1-fold different than a reference level of the CERS3 polypeptide (or a reference level of an mRNA encoding a CERS3 polypeptide).
  • an increased level of an mRNA encoding a CERS3 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a CERS3 polypeptide.
  • a decreased level of an mRNA encoding a CERS3 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a CERS3 polypeptide.
  • an altered level of a polypeptide can be an altered level (e.g., an increased level increased level or a decreased level) of a NQO1 polypeptide (or an altered level of an mRNA encoding a NQO1 polypeptide).
  • An example of a NQO1 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, NP_000894.1 (version NP_000894.1).
  • an altered level of a NQO1 polypeptide can be any level that is at least 1- fold different than a reference level of the NQO1 polypeptide (or a reference level of an mRNA encoding a NQO1 polypeptide).
  • an increased level of an mRNA encoding a NQO1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a NQO1 polypeptide.
  • a decreased level of an mRNA encoding a NQO1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a NQO1 polypeptide.
  • an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of an ALDH1A1 polypeptide Attorney Docket No.07039-2153WO1 / 2022-168 (or an altered level of an mRNA encoding an ALDH1A1 polypeptide).
  • an ALDH1A1 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, NP_000680 (version NP_000680.2).
  • an altered level of an ALDH1A1 polypeptide can be any level that is at least 1-fold different than a reference level of the ALDH1A1 polypeptide (or a reference level of an mRNA encoding an ALDH1A1 polypeptide).
  • an increased level of an mRNA encoding an ALDH1A1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding an ALDH1A1 polypeptide.
  • a decreased level of an mRNA encoding an ALDH1A1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding an ALDH1A1 polypeptide.
  • any appropriate method can be used to determine the presence, absence, or level of a polypeptide or mRNA encoding that polypeptide.
  • the presence, absence, or level of an mRNA encoding a polypeptide can be assessed by detecting and/or quantifying the mRNA encoding a polypeptide.
  • methods that can be used to detect and/or quantify mRNA include, without limitation, RT-PCR techniques (e.g., quantitative RT-PCR techniques), bulk RNA-seq technology platforms, and NanoString platforms.
  • the presence, absence, or level of a polypeptide can be assessed by detecting and/or quantifying the polypeptide.
  • Examples of methods that can be used to detect and/or quantify polypeptides include, without limitation, immunohistochemistry (IHC) techniques, mass spectrometry techniques (e.g., proteomics-based mass spectrometry assays or targeted quantification-based mass spectrometry assays), and western blotting techniques.
  • IHC immunohistochemistry
  • mass spectrometry techniques e.g., proteomics-based mass spectrometry assays or targeted quantification-based mass spectrometry assays
  • western blotting techniques e.g., Western blotting techniques.
  • the presence, absence, or level of a polypeptide and/or mRNA encoding that polypeptide can be identified as described in Example 1, Example 2, Example 3, or Example 4.
  • Any appropriate sample from a mammal (e.g., a human) having a cSCC can be assessed as described herein (e.g., for the molecular signature of the cSCC).
  • a sample can be a biological sample.
  • a sample can contain one or more cancer Attorney Docket No.07039-2153WO1 / 2022-168 cells (e.g., cSCC cells).
  • a sample can contain one or more biological molecules (e.g., nucleic acids such as DNA and RNA, polypeptides, carbohydrates, lipids, hormones, and/or metabolites). Examples of samples that can be assessed as described herein include, without limitation, tissue samples (e.g., skin samples).
  • a sample can be a fresh sample or a fixed sample (e.g., a formaldehyde-fixed sample or a formalin-fixed sample).
  • one or more biological molecules can be isolated from a sample (e.g., from one or more cancer cells within the sample).
  • nucleic acid can be isolated from a sample and can be assessed as described herein.
  • polypeptides can be isolated from a sample and can be assessed as described herein.
  • the molecular signature of a cSCC can be used to identify a mammal (e.g., a human) having the cSCC as being likely to experience prolonged survival from cSCC (e.g., prolonged survival from the time of cSCC diagnosis).
  • an altered level of a BIRC5 polypeptide or mRNA encoding a BIRC5 polypeptide
  • an altered level of a MELK polypeptide or mRNA encoding a MELK polypeptide
  • an altered level of an IFNE polypeptide or mRNA encoding an IFNE polypeptide
  • an altered level of a HMGCS1 polypeptide or mRNA encoding a HMGCS1 polypeptide
  • an altered level of an ANK2 polypeptide or mRNA encoding an ANK2 polypeptide
  • an altered level of a LAMA2 polypeptide or mRNA encoding a LAMA2 polypeptide
  • an altered level of a CYP2U1 polypeptide or mRNA encoding a CYP2U1 polypeptide
  • an altered level of a FAM13C polypeptide or mRNA encoding a FAM13C polypeptide
  • an altered level of a FAM13C polypeptide or m
  • each of an altered level of a BIRC5 polypeptide or mRNA encoding a BIRC5 polypeptide
  • an altered level of a MELK polypeptide or mRNA encoding a MELK polypeptide
  • an altered level of an IFNE polypeptide or mRNA encoding an IFNE polypeptide
  • an altered level of a HMGCS1 polypeptide or mRNA encoding a HMGCS1 polypeptide
  • an altered level of an ANK2 polypeptide or mRNA encoding an ANK2 polypeptide
  • an altered level of a LAMA2 polypeptide or mRNA encoding a LAMA2 polypeptide
  • an altered level of a CYP2U1 polypeptide or mRNA encoding a CYP2U1 polypeptide
  • an altered level of a FAM13C polypeptide or mRNA encoding a FAM13C polypeptide
  • each of an altered level of an ACSL1 polypeptide or mRNA encoding an ACSL1 polypeptide
  • an altered level of an ALDH1A1 polypeptide or mRNA encoding an ALDH1A1 polypeptide
  • an altered level of an ALDH3A2 polypeptide or mRNA encoding an ALDH3A2 polypeptide
  • an altered level of an ALOX12 polypeptide or mRNA encoding an ALOX12 Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide
  • an altered level of a CALCOCO1 polypeptide or mRNA encoding a CALCOCO1 polypeptide
  • an altered level of a CASP14 polypeptide or mRNA encoding a CASP14 polypeptide
  • an altered level of a CDC6 polypeptide or mRNA encoding a CDC6 polypeptide
  • an altered level of a CDCA5 polypeptide or mRNA
  • each of an altered level of an ACSL1 polypeptide or mRNA encoding an ACSL1 polypeptide
  • an altered level of an ALDH3A2 polypeptide or mRNA encoding an ALDH3A2 polypeptide
  • an altered level of an ALOX12 polypeptide or mRNA encoding an ALOX12 polypeptide
  • an altered level of a CALCOCO1 polypeptide or mRNA encoding a CALCOCO1 polypeptide
  • an altered level of a CASP14 polypeptide or mRNA encoding a CASP14 polypeptide
  • an altered level of a CDCA5 polypeptide or mRNA encoding a CDCA5 polypeptide
  • an altered level of a CEP55 polypeptide or mRNA encoding a CEP55 polypeptide
  • an altered level of a CXCL8 polypeptide or mRNA encoding a CXCL8 polypeptide
  • each of an altered level of an ALDH1A1 polypeptide (or mRNA encoding an ALDH1A1 polypeptide), an altered level of an ALDH3A2 polypeptide (or mRNA encoding an ALDH3A2 polypeptide), an altered level of an ALOX12 polypeptide (or mRNA encoding an ALOX12 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of a CDCA5 polypeptide (or mRNA encoding a CDCA5 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a NQO1 polypeptide (or mRNA encoding a NQO1 polypeptide), an altered level of a TSGA10 polypeptide (or mRNA encoding a TSGA10 polypeptide), and an altered level of a Z
  • the molecular signature of a cSCC can be used to identify a mammal (e.g., a human) having the cSCC as not being likely to experience prolonged survival from cSCC (e.g., prolonged survival from the time of cSCC diagnosis).
  • a mammal e.g., a human having a cSCC that is identified as being likely to experience prolonged survival from cSCC (e.g., prolonged survival from the time of cSCC diagnosis) as described herein (e.g., based, at least in part, on the molecular signature of the cSCC) can be selected to receive surgery to remove the cSCC.
  • a mammal e.g., a human having a cSCC that is identified as being likely to experience prolonged survival from cSCC (e.g., prolonged survival from the time of cSCC diagnosis) as described herein (e.g., based, at least in part, on the molecular signature of the cSCC) can be selected to receive surgery to remove the cSCC.
  • a mammal having a cSCC that is identified as having a molecular signature that includes the presence of one or more of an altered level of a BIRC5 polypeptide (or mRNA encoding a BIRC5 polypeptide), an altered level of a MELK polypeptide (or mRNA encoding a MELK polypeptide), an altered level of an IFNE polypeptide (or mRNA encoding an IFNE polypeptide), an altered level of a HMGCS1 polypeptide (or mRNA encoding a HMGCS1 polypeptide), an altered level of an ANK2 polypeptide (or mRNA encoding an ANK2 polypeptide), an altered level of a LAMA2 polypeptide (or mRNA encoding a LAMA2 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 Attorney Docket No.07039-2153WO1 / 2022
  • a mammal e.g., a human having a cSCC and identified as being unlikely to experience prolonged survival from cSCC (e.g., prolonged survival from the time of cSCC diagnosis) as described herein (e.g., based, at least in part, on the molecular signature of the cSCC) can be selected to receive surgery to remove the cSCC and can be selected for increased monitoring.
  • a mammal e.g., a human having a cSCC and identified as being unlikely to experience prolonged survival from cSCC (e.g., prolonged survival from the time Attorney Docket No.07039-2153WO1 / 2022-168 of cSCC diagnosis) as described herein (e.g., based, at least in part, on the molecular signature of the cSCC) can be selected to receive surgery to remove the cSCC and can be selected for treatment with one or more adjuvant therapies.
  • a mammal having a cSCC that is identified as having a molecular signature that lacks the presence of one or more of an altered level of a BIRC5 polypeptide (or mRNA encoding a BIRC5 polypeptide), an altered level of a MELK polypeptide (or mRNA encoding a MELK polypeptide), an altered level of an IFNE polypeptide (or mRNA encoding an IFNE polypeptide), an altered level of a HMGCS1 polypeptide (or mRNA encoding a HMGCS1 polypeptide), an altered level of an ANK2 polypeptide (or mRNA encoding an ANK2 polypeptide), an altered level of a LAMA2 polypeptide (or mRNA encoding a LAMA2 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a FAM13C polypeptid
  • the molecular signature of a cSCC can be used to identify the cSCC as being likely to metastasize. For example, the presence of one or more of an altered level of a CSAG1 polypeptide (or mRNA encoding a CSAG1 polypeptide), an altered level of an UBE2C polypeptide (or mRNA encoding an UBE2C polypeptide), an altered level of an ANKRD1 polypeptide (or mRNA encoding an ANKRD1 polypeptide), an altered level of a CSMD3 polypeptide (or mRNA encoding a CSMD3 polypeptide), an altered level of a TOP2A polypeptide (or mRNA encoding a TOP2A polypeptide), an altered level of a TPX2 polypeptide (or mRNA encoding a TPX2 polypeptide), an altered level of a KSR2 polypeptide (or mRNA encoding a KSR2 polypeptide), an altered level of
  • an altered level of a CSAG1 polypeptide (or mRNA encoding a CSAG1 polypeptide), an altered level of an UBE2C polypeptide (or mRNA encoding an UBE2C polypeptide), an altered level of an ANKRD1 polypeptide (or mRNA encoding an ANKRD1 polypeptide), an altered level of a CSMD3 polypeptide (or mRNA encoding a CSMD3 polypeptide), an altered level of a TOP2A polypeptide (or mRNA encoding a TOP2A polypeptide), an altered level of a TPX2 polypeptide (or mRNA encoding a TPX2 polypeptide), an altered level of a KSR2 polypeptide (or mRNA encoding a KSR2 polypeptide), an altered level of a CSMD2 polypeptide (or mRNA encoding a CSMD2 polypeptide), an altered level of a MMP
  • an altered level of an altered level of a Attorney Docket No.07039-2153WO1 / 2022-168 CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of a FN1 polypeptide (or mRNA encoding a FN1 polypeptide), an altered level of a MGAM polypeptide (or mRNA encoding a MGAM polypeptide), an altered level of an EVPL polypeptide (or mRNA encoding an EVPL polypeptide), an altered level of an AOX1 polypeptide (or mRNA encoding an AOX1 polypeptide), an altered level of a PLA2R1 polypeptide (or mRNA
  • the molecular signature of a cSCC can be used to identify a cSCC as not being likely to metastasize. For example, the absence of an altered level of a CSAG1 polypeptide (or mRNA encoding a CSAG1 polypeptide), an altered level of an UBE2C polypeptide (or mRNA encoding an UBE2C polypeptide), an altered level of an ANKRD1 polypeptide (or mRNA encoding an ANKRD1 polypeptide), an altered level of a CSMD3 polypeptide (or mRNA encoding a CSMD3 polypeptide), an altered level of a TOP2A polypeptide (or mRNA encoding a TOP2A polypeptide), an altered level of a TPX2 polypeptide (or mRNA encoding a TPX2 polypeptide), an altered level of a KSR2 polypeptide (or mRNA encoding a KSR2 polypeptide), an altered level of
  • a mammal e.g., a human having a cSCC that is identified as not being likely to metastasize (e.g., not likely to metastasize to one or more lymph nodes) as Attorney Docket No.07039-2153WO1 / 2022-168 described herein (e.g., based, at least in part, on the molecular signature of the cSCC) can be selected to receive surgery to remove the cSCC.
  • a mammal having a cSCC that is identified as having a molecular signature that lacks an altered level of a CSAG1 polypeptide (or mRNA encoding a CSAG1 polypeptide), an altered level of an UBE2C polypeptide (or mRNA encoding an UBE2C polypeptide), an altered level of an ANKRD1 polypeptide (or mRNA encoding an ANKRD1 polypeptide), an altered level of a CSMD3 polypeptide (or mRNA encoding a CSMD3 polypeptide), an altered level of a TOP2A polypeptide (or mRNA encoding a TOP2A polypeptide), an altered level of a TPX2 polypeptide (or mRNA encoding a TPX2 polypeptide), an altered level of a KSR2 polypeptide (or mRNA encoding a KSR2 polypeptide), an altered level of a CSMD2 polypeptide (or mM
  • a mammal e.g., a human having a cSCC that is identified as being likely to metastasize (e.g., likely to metastasize to one or more lymph nodes) as described herein (e.g., based, at least in part, on the molecular signature of the cSCC) can be selected to receive surgery to remove the cSCC and can be selected for increased monitoring.
  • a mammal e.g., a human having a cSCC that is identified as being likely to metastasize (e.g., likely to metastasize to one or more lymph nodes) as described herein (e.g., based, at least in part, on the molecular signature of the cSCC) can be selected to receive surgery to remove the cSCC and can be selected for increased monitoring.
  • a mammal having a cSCC that is identified as having a molecular signature that includes one or more of an altered level of a CSAG1 polypeptide (or mRNA encoding a CSAG1 polypeptide), an altered level of an UBE2C polypeptide (or mRNA encoding an UBE2C polypeptide), an altered level of an ANKRD1 polypeptide (or mRNA encoding an ANKRD1 polypeptide), an altered level of a CSMD3 polypeptide (or mRNA encoding a CSMD3 polypeptide), an altered level of a TOP2A polypeptide (or mRNA encoding a TOP2A polypeptide), an altered level of a TPX2 polypeptide (or mRNA encoding a TPX2 polypeptide), an altered level of a KSR2 polypeptide (or mRNA encoding a KSR2 polypeptide), an altered level of a CSMD2 polypeptide (
  • a mammal e.g., a human having a cSCC that is identified as being likely to metastasize (e.g., likely to metastasize to one or more lymph nodes) as described herein (e.g., based, at least in part, on the molecular signature of the cSCC) can be selected to receive surgery to remove the cSCC and can be selected for treatment with one or more adjuvant therapies.
  • a mammal e.g., a human having a cSCC that is identified as being likely to metastasize (e.g., likely to metastasize to one or more lymph nodes) as described herein (e.g., based, at least in part, on the molecular signature of the cSCC) can be selected to receive surgery to remove the cSCC and can be selected for treatment with one or more adjuvant therapies.
  • a mammal having a cSCC that is identified as having a molecular signature that includes one or more of an altered level of a CSAG1 polypeptide (or mRNA encoding a CSAG1 polypeptide), an altered level of an UBE2C polypeptide (or mRNA encoding an UBE2C polypeptide), an altered level of an ANKRD1 polypeptide (or mRNA encoding an ANKRD1 polypeptide), an altered level of a CSMD3 polypeptide (or mRNA encoding a CSMD3 polypeptide), an altered level of a TOP2A polypeptide (or mRNA encoding a TOP2A polypeptide), an altered level of a TPX2 polypeptide (or mRNA Attorney Docket No.07039-2153WO1 / 2022-168 encoding a TPX2 polypeptide), an altered level of a KSR2 polypeptide (or mRNA encoding a KSR
  • a mammal having a cSCC that is identified as having a molecular signature that includes one or more of an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of a FN1 polypeptide (or mRNA encoding a FN1 polypeptide), an altered level of a MGAM polypeptide (or mRNA encoding a MGAM polypeptide), an altered level of an EVPL polypeptide (or mRNA encoding an EVPL polypeptide), an altered level of an AOX1 polypeptide (or mRNA encoding an AOX1 polypeptide), an altered level of a PLA2R1 polypeptide (or
  • This document also provides methods for treating a mammal (e.g., a human) having cSCC.
  • a mammal e.g., a human having a cSCC and assessed as described herein (e.g., to determine whether or not the mammal is likely to experience prolonged survival from cSCC (e.g., prolonged survival from the time of cSCC diagnosis) based, at least in part, on the molecular signature of the cSCC and/or to determine whether or not the cSCC is likely to metastasize based, at least in part, on the molecular signature of the cSCC) can be administered or instructed to self-administer one or more (e.g., one, two, three, four, five, or more) cancer treatments, where the one or more cancer treatments are effective to treat the cancer within the mammal.
  • one or more cancer treatments e.g., one, two, three, four, five, or more
  • a mammal having a cSCC can be administered or instructed to self-administer one or more cancer treatments selected based, at least in part, on whether or not the cSCC is likely to metastasize (e.g., based, at least in part, on the molecular signature of the cSCC).
  • a cancer treatment for cSCC can include any appropriate cSCC treatment.
  • a cancer treatment for cSCC can include surgery and other medical interventions.
  • a cancer treatment can include administering one or more anti-cancer drugs (e.g., chemotherapeutic agents, targeted cancer drugs, and immunotherapy drugs) to a mammal in need thereof.
  • an anti-cancer drug can be an EGFR inhibitor.
  • anti-cancer drugs that can be administered to a mammal having a cSCC can include, without limitation, cemiplimab-rwlc (e.g., LIBTAYO ® ), nivolumab (e.g., OPDIVO ® ), ipilimumab (e.g., YERVOY ® ), pembrolizumab (e.g., KEYTRUDA ® ), talimogene laherparepvec (T-VEC; e.g., IMLYGIC ® ), cetuximab (e.g., ERBITUX), capecitabine (e.g., XELODA ® ), (5-FU), and combinations thereof.
  • cemiplimab-rwlc e.g., LIBTAYO ®
  • nivolumab e.g., OPDIVO ®
  • ipilimumab
  • a mammal having a cSCC that is identified as having a molecular signature that includes the presence of one or more an altered level of a BIRC5 polypeptide (or mRNA encoding a BIRC5 polypeptide), an altered level of a MELK polypeptide (or mRNA encoding a MELK polypeptide), an altered level of an IFNE polypeptide (or mRNA encoding an IFNE polypeptide), an altered level of a HMGCS1 polypeptide (or mRNA encoding a HMGCS1 polypeptide), an altered level of an ANK2 polypeptide (or mRNA encoding an ANK2 polypeptide), an altered level of a LAMA2 polypeptide (or mRNA encoding a LAMA2 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a FAM13C polypeptide (
  • a mammal e.g., a human
  • the mammal can undergo surgery to remove the cSCC and can be administered or instructed to self-administer one or more adjuvant therapies.
  • a mammal having a cSCC that is identified as having a molecular signature that lacks the presence of an altered level of a BIRC5 polypeptide (or mRNA encoding a BIRC5 polypeptide), an altered level of a MELK polypeptide (or mRNA encoding a MELK polypeptide), an altered level of an IFNE polypeptide (or mRNA encoding an IFNE polypeptide), an altered level of a HMGCS1 polypeptide (or mRNA encoding a HMGCS1 polypeptide), an altered level of an ANK2 polypeptide (or mRNA encoding an ANK2 polypeptide), an altered level of a LAMA2 polypeptide (or mRNA encoding a LAMA2 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a FAM13C polypeptide (or
  • a mammal e.g., a human
  • a cSCC identified as not being likely to metastasize as described herein e.g., based, at least in part, on the molecular signature of the cSCC
  • the mammal can undergo surgery to remove the cSCC.
  • a mammal having a cSCC that is identified as having a molecular signature that lacks an altered level of a CSAG1 polypeptide (or mRNA encoding a CSAG1 polypeptide), an altered level of an UBE2C polypeptide (or mRNA encoding an UBE2C polypeptide), an altered level of an ANKRD1 polypeptide (or mRNA encoding an ANKRD1 polypeptide), an altered level of a CSMD3 polypeptide (or mRNA encoding a CSMD3 polypeptide), an altered level of a TOP2A polypeptide (or mRNA encoding a TOP2A polypeptide), an altered level of a TPX2 polypeptide (or mRNA encoding a TPX2 polypeptide), an altered level of a KSR2 polypeptide (or mRNA encoding a KSR2 polypeptide), an altered level of a CSMD2 polypeptide (or mM
  • a mammal e.g., a human
  • a cSCC identified as being likely to metastasize as described herein (e.g., based, at least in part, on the molecular signature of the cSCC)
  • the mammal can undergo surgery to remove the cSCC and can be administered or instructed to self-administer one or more adjuvant therapies.
  • a mammal having a cSCC that is identified as having a molecular signature that includes one or more of an altered level of a CSAG1 polypeptide (or mRNA encoding a CSAG1 polypeptide), an altered level of an UBE2C polypeptide (or mRNA encoding an UBE2C polypeptide), an altered level of an ANKRD1 polypeptide (or mRNA encoding an ANKRD1 polypeptide), an altered level of a CSMD3 polypeptide (or mRNA encoding a CSMD3 polypeptide), an altered level of a TOP2A polypeptide (or mRNA encoding a TOP2A polypeptide), an altered level of a TPX2 polypeptide (or mRNA encoding a TPX2 polypeptide), an altered level of a KSR2 polypeptide (or mRNA encoding a KSR2 polypeptide), an altered level of a CSMD2 Attorney Docket
  • An adjuvant therapy can be any appropriate cancer treatment.
  • a cancer treatment that can be used as an adjuvant therapy with surgery to treat a mammal e.g., a Attorney Docket No.07039-2153WO1 / 2022-168 human
  • a mammal e.g., a Attorney Docket No.07039-2153WO1 / 2022-168 human
  • having a cSCC and identified as not being likely to experience prolonged survival from cSCC e.g., prolonged survival from the time of cSCC diagnosis
  • a cSCC that is likely to metastasize as described herein (e.g., based, at least in part, on the molecular signature of the cSCC)
  • radiation therapy e.g., radiation therapy.
  • a cancer treatment that can be used as an adjuvant therapy with surgery to treat a mammal having a cSCC and identified as not being likely to experience prolonged survival from cSCC as described herein and/or identified as having a cSCC that is likely to metastasize as described herein can include administering one or more anti-cancer drugs (e.g., chemotherapeutic agents, targeted cancer drugs, and immunotherapy drugs) to the mammal.
  • anti-cancer drugs e.g., chemotherapeutic agents, targeted cancer drugs, and immunotherapy drugs
  • anti-cancer drugs that can be administered to a mammal having a cSCC can include, without limitation, cemiplimab-rwlc (e.g., LIBTAYO ® ), nivolumab (e.g., OPDIVO ® ), ipilimumab (e.g., YERVOY ® ), pembrolizumab (e.g., KEYTRUDA ® ), talimogene laherparepvec (T-VEC; e.g., IMLYGIC ® ), cetuximab (e.g., ERBITUX), capecitabine (e.g., XELODA ® ), carboplatin, 5-FU, and combinations thereof.
  • cemiplimab-rwlc e.g., LIBTAYO ®
  • nivolumab e.g., OPDIVO ®
  • the treatment when treating a mammal (e.g., a human) having a cSCC as described herein, the treatment can be effective to treat the cSCC.
  • the number of cancer cells present within a mammal can be reduced using the methods and materials described herein.
  • the methods and materials described herein can be used to reduce the number of cancer cells present within a mammal having a cSCC by, for example, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, or more percent.
  • the number of cancer cells present within a mammal does not increase.
  • the size (e.g., volume) of one or more tumors present within a mammal can be reduced using the methods and materials described herein.
  • the methods and materials described herein can be used to reduce the size of one or more tumors present within a mammal having a cSCC by, for example, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, or more percent. In some cases, the size (e.g., volume) of one or more tumors present within a mammal does not increase. In some cases, when treating a mammal (e.g., a human) having a cSCC as described herein, the treatment can be effective to treat the cSCC while minimizing the risk of metastasis.
  • a mammal e.g., a human
  • the treatment when treating a mammal (e.g., a human) having a cSCC as described herein, the treatment can be effective to improve survival of the mammal.
  • a mammal e.g., a human
  • the treatment can be effective to improve survival of the mammal.
  • a Attorney Docket No.07039-2153WO1 / 2022-168 mammal e.g., a human
  • having a cSCC and identified as being likely to experience prolonged survival from cSCC e.g., prolonged survival from the time of cSCC diagnosis
  • a higher survival rate e.g., based, at least in part, on the molecular signature of the cSCC
  • a mammal having a cSCC that is identified as having a molecular signature that includes the presence of one or more of an altered level of a BIRC5 polypeptide (or mRNA encoding a BIRC5 polypeptide), an altered level of a MELK polypeptide (or mRNA encoding a MELK polypeptide), an altered level of an IFNE polypeptide (or mRNA encoding an IFNE polypeptide), an altered level of a HMGCS1 polypeptide (or mRNA encoding a HMGCS1 polypeptide), an altered level of an ANK2 polypeptide (or mRNA encoding an ANK2 polypeptide), an altered level of a LAMA2 polypeptide (or mRNA encoding a LAMA2 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a FAM13C polypeptide
  • a prolonged survival from cSCC can be survival (e.g., overall survival or disease-free survival) that is longer than 2 years (e.g., from the diagnosis of the cSCC).
  • survival e.g., overall survival or disease-free survival
  • the methods and materials described herein can be used to improve survival (e.g., overall survival or disease-free survival).
  • overall survival e.g., overall survival or disease-free survival
  • the methods and materials described herein can be used to improve overall survival.
  • the methods and materials described herein can be used to improve the survival of a mammal having a cSCC by, for example, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, or more percent.
  • the methods and materials described herein can be used to improve the survival of a mammal having a cSCC by, for example, at least 6 months (e.g., about 6 months, about 8 months, about 10 months, about 1 year, about 1.5 years, about 2 years, about 2.5 years, or about 3 years).
  • the treatment can be effective to improve survival of the mammal while minimizing the risk of metastasis.
  • the treatment can be effective to reduce or eliminate one or more symptoms of the cSCC.
  • Examples of symptoms of cSCC that can be reduced or eliminated using the methods and materials described herein can include, without limitation, firm and red nodules, flat sores (e.g., with a scaly crust), raised areas on old scars, ulcers, rough patches on the lip and/or inside the mouth, scaly patches on the lip, open sores on the lip and/or inside the mouth, pain, and swelling (e.g., lymphedema).
  • the methods and materials described herein can be used to reduce one or more symptoms of cSCC within a mammal having a cSCC by, for example, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, or more percent.
  • the treatment when treating a mammal (e.g., a human) having a cSCC as described herein, the treatment can be effective to reduce or eliminate one or more symptoms of the cSCC while minimizing the risk of metastasis.
  • a course of treatment the number of cancer cells present within a mammal and/or the severity of one or more symptoms related to the cSCC can be monitored. Any appropriate method can be used to determine whether or not the number of cancer cells present within a mammal is reduced. For example, imaging techniques can be used to assess the number of cancer cells present within a mammal.
  • Example 1 Metastatic Potential of cSCC This example describes the identification of a gene expression signature for cSCC that can be used to predict whether or not a cSCC patient is at a higher risk of metastasis (e.g., nodal metastasis). Integrated genomics and transcriptomics of matched samples of intermediate and high-risk (T2a & T2b, as classified by Brigham Women’s Hospital Staging) cSCC were performed.
  • Each marker was identified based on having at least 1-fold change on the Log 2 normalized data (log2 fold change), which means 1-fold change in the normalized data was twofold change in the gene expression raw count data in RNA-seq.
  • the significance of changes in genes was assessed using DEseq2 R software package using a negative binomial GLM to test each gene.
  • the markers were selected based on two criteria: (1) log2 fold change > 1 (upregulated) or ⁇ -1 (downregulated), and (2) p values from the negative binomial GLM model ⁇ 0.05 which was adjusted for multiple testing for correcting false positive rate (adjusted p values ⁇ 0.05).
  • the housekeeping genes used to identify markers are shown in Table 1 and were selected based on the following characteristics: 1) gene expression level was no different between the cancer and control groups (e.g., based on FDR-adjusted p values), 2) variation in the genes was relatively small (e.g., less than 1 in the log2 normalized expression data), 3) gene expression was at a detectable level (e.g., higher than 85% of all genes in the RNA-seq cohort (>10)), and 4) protein-coding genes. Table 1. House-keeping genes used to determine differential expression.
  • the assay properly stratifies 95% of non-metastatic intermediate to high risk tumors and 70% of metastatic intermediate to high risk tumors.
  • an increased level of a NXF1 polypeptide (or mRNA encoding a NXF1 polypeptide), an increased level of a CENPO polypeptide (or mRNA encoding a CENPO polypeptide), an increased level of a CXCL10 polypeptide (or mRNA encoding a CXCL10 polypeptide), an increased level of a CXCL11 polypeptide (or mRNA encoding a CXCL11 polypeptide), an increased level of a CXCL9 polypeptide (or mRNA encoding a CXCL9 polypeptide), an increased level of an OAS2 polypeptide (or mRNA encoding an OAS2 polypeptide), an increased level of a LAMA2 polypeptide (or mRNA Attorney Docket No.07039-2153WO1 / 2022-168 encoding a LAMA2 polypeptide), and/or an increased level of a MYRIP polypeptide (or mRNA encoding a M
  • an increased level of an ABCA12 polypeptide (or mRNA encoding an ABCA12 polypeptide), an increased level of a FLG2 polypeptide (or mRNA encoding a FLG2 polypeptide), an increased level of a LCE2D polypeptide (or mRNA encoding a LCE2D polypeptide), an increased level of a LOR polypeptide (or mRNA encoding a LOR polypeptide), an increased level of a RGL3 polypeptide (or mRNA encoding a RGL3 polypeptide), an increased level of an OASL polypeptide (or mRNA encoding an OASL polypeptide), and/or an increased level of an INMT polypeptide (or mRNA encoding an INMT polypeptide), in a cancer cells of a mammal (e.g., a human) having a cSCC can be used to identify that cSCC as being likely to metastasize (e.g., likely to
  • Example 2 cSCC RNA analysis This analysis looked at the differential expression levels of 183 genes – 50 were up- regulated, 50 were down-regulated, and 14 differed between metastatic and non-metastatic samples. Additional genes were differentially expressed from MutSig and OncoDrive analyses. For all the RNA sample data, the primary control sample data were removed. For patients with multiple primary tumor data, the 1st primary tumor sample data was used and subsequent sample data were excluded. Therefore, this analysis used a total of 50 patients (22 metastatic patients and 28 non-metastatic patients).
  • Clustering analysis A partitioning around medoids (PAM) method was used to cluster the 183 genes into 9 clusters: 26 genes in cluster 1, 12 genes in cluster 2, 9 genes in cluster 3, 50 genes in cluster 4, 18 genes in cluster 5, 22 genes in cluster 6, 20 genes in cluster 7, 15 genes in cluster 8, and 11 genes in cluster 9. The genes were ordered based on their cluster order, and a heatmap was generated based on the Pearson correlation coefficients using their raw expression data. Genes within Attorney Docket No.07039-2153WO1 / 2022-168 cluster 1, 4, 5 and 6 were highly correlated with each other, genes within cluster 2 and 3 were moderately correlated with each other, and genes in clusters 7, 8, 9 were weakly correlated with each other ( Figure 1).
  • Patient Population Table 2 shows the patient demographics and clinical characteristics of metastatic patients (PMet) and non-metastatic patients (PNoMet). There was no significant difference in age at CSCC onset, sex, race, immunosuppressant use, or disease stage between the two groups. Table 2. Patient demographics and clinical characteristics. Attorney Docket No.07039-2153WO1 / 2022-168 Gene summary statistics Table 3 shows the categorical data for each gene including demographics, clinical characteristics, and gene mutations by metastasic status. Table 3. Demographics, Clinical Characteristics, and Gene Mutations Comparison.
  • CSAG1, UBE2C, ANKRD1, CSMD3, TOP2A, TPX2, KSR2, CSMD2, MMP20, PCSK1, TMEM150B, ACSL1, TSGA10, KIT, RGL3, and PLA2G6 were used to generate the risk score for metastasis. Table 4 summarized the generation of the risk score.
  • the AUC area under ROC curve
  • Figure 2 A risk score of 9 was as a cut-off to predict metastasis. Patients who had a risk score of 9 or above were considered as having metastasis, while patients who had a risk score 8 or below were considered as not having metastasis. The sensitivity, specificity and overall accuracy for this cut-off were 95.5%, 85.7%, and 90%, respectively. Table 4. Risk score comparison.
  • BIRC5, MELK, IFNE, HMGCS1, ANK2, LAMA2, CYP2U1, FAM13C, COL25A1, TG, and FAT4 were used to generate a risk score for overall survival.
  • the risk score based on these genes stratified the patients very well for their overall survival ( Figures 3-5 and Table 5).
  • the median survival time for patients with risk score ⁇ 4 was 8.9 years
  • median survival time for patients with risk score between 5 and Attorney Docket No.07039-2153WO1 / 2022-168 7 was 3.9 years and for patients with risk score 8 and above was 1.6 years.
  • an altered level of a CSAG1 polypeptide (or mRNA encoding a CSAG1 polypeptide), an altered level of an UBE2C polypeptide (or mRNA encoding an UBE2C polypeptide), an altered level of an ANKRD1 polypeptide (or mRNA encoding an ANKRD1 polypeptide), an altered level of a CSMD3 polypeptide (or mRNA encoding a CSMD3 polypeptide), an altered level of a TOP2A polypeptide (or mRNA encoding a TOP2A polypeptide), an altered level of a TPX2 polypeptide (or mRNA encoding a TPX2 polypeptide), an altered level of a KSR2 polypeptide (or mRNA encoding a KSR2 polypeptide), an altered level of a CSMD2 polypeptide (or mRNA encoding a CSMD2 polypeptide), an altered level of a MMP20 polypeptide
  • an altered level of a BIRC5 polypeptide (or mRNA encoding a BIRC5 polypeptide), an altered level of a MELK polypeptide (or mRNA encoding a MELK polypeptide), an altered level of an IFNE polypeptide (or mRNA encoding an IFNE polypeptide), an altered level of a HMGCS1 polypeptide (or mRNA encoding a HMGCS1 polypeptide), an altered level of an ANK2 polypeptide (or mRNA encoding an ANK2 polypeptide), an altered level of a LAMA2 polypeptide (or mRNA encoding a LAMA2 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a FAM13C polypeptide (or mRNA encoding a FAM13C polypeptide), an altered level of a COL25A1 polypeptid
  • Example 3 cSCC RNA analysis This analysis looked at the differential expression levels of genes to determine a molecular signature between metastatic and non-metastatic samples, with a total of 186 samples from 183 subjects (3 subjects provided 2 samples each). The results in this Example re-present and expand on at least some of the results provided in other Examples.
  • Figure 6 shows the differential gene expression of the 186 samples studied. The genes included are predictive of outcome including metastasis and survival. Differences were seen between metastatic and non-metastatic tumors across these genes of interest.
  • Attorney Docket No.07039-2153WO1 / 2022-168 Patient Population Table 6 shows the patients’ demographics and clinical characteristics of the metastatic (Met) group compared to non-metastatic (No Met) group.
  • Table 7 shows the tumor characteristic by metastatic (Met) group compared to non- metastatic (No Met) group. There was no significant difference in terms of age at biopsy and tumor stage between the two groups (although the tumor stage was only available for the internal samples). Table 6.
  • CDCA5 genes were considered – CDCA5, CXCL8, PRC1 and ZNF750 (these 4 genes up-regulated were associated with worse survival), KRT2, ALOX12, ALDH3A2, and DMD (these 4 genes down-regulated were associated with worse survival), NQO1, ACAT2, CSMD2, CMYA5, CXCL10 (these 5 genes were not significantly associated with worse survival, so they were not used in the analysis).
  • the other 8 genes (CDCA5, CXCL8, PRC1, ZNF750, KRT2, ALOX12, ALDH3A2, and DMD) were chosen to generate the risk score for overall survival. The risk scores for overall survival were significantly different between Met and Non-Met groups (p ⁇ .001, Table 9).
  • the risk score based on the 8 genes stratified the patients for their overall survival ( Figures 10A-10B and Table 11).
  • the risk of death increased by 1.28 (HR: 1.28, 95% CI: 1.13 to 1.46, p ⁇ .001) after adjusting for age, immunosuppressant use, and metastasis status.
  • the Harrell’s C- statistic for the risk score to predict OS was 65.6%.
  • the median event-free survival time for patients with risk score 0 was 7.8 years
  • median event-free survival time for patients with risk score between 2 and 5 was 2.1 years
  • for patients with risk score between 6 and 8 was 0.2 years.
  • the Harrell’s C-statistic for the risk score to predict OS was 66.6%.
  • an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of an CYP2U1 polypeptide (or mRNA encoding an CYP2U1 polypeptide), an altered level of an FN1 polypeptide (or mRNA encoding an FN1 polypeptide), an altered level of a MGAM polypeptide (or mRNA encoding a MGAM polypeptide), an altered level of a KIT polypeptide (or mRNA encoding a KIT polypeptide), an altered level of a CYP2E1 polypeptide (or mRNA encoding a CYP2E1 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a
  • an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of an CYP2U1 polypeptide (or mRNA encoding an CYP2U1 polypeptide), an altered level of an FN1 polypeptide (or mRNA encoding an FN1 polypeptide), an altered level of a MGAM polypeptide (or mRNA encoding a MGAM polypeptide), an altered level of a KIT polypeptide (or mRNA encoding a KIT polypeptide), an altered level of a CYP2E1 polypeptide (or mRNA encoding a CYP2E1 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a
  • an altered level of a CXCL8 polypeptide (or mRNA encoding a CXCL8 polypeptide), an altered level of an ZNF750 polypeptide (or mRNA encoding an ZNF750 polypeptide), an altered level of an CDCA5 polypeptide (or mRNA encoding an CDCA5 polypeptide), an altered level of a PRC1 polypeptide (or mRNA encoding a PRC1 polypeptide), an altered level of a KRT2 polypeptide (or mRNA encoding a KRT2 polypeptide), an altered level of a ALOX12 polypeptide (or mRNA encoding a ALOX12 polypeptide), an altered level of a ALOX12 polypeptide (or mRNA encoding a ALOX12 polypeptide), and/or an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), in a cancer cells of a mammal (e.g.
  • an altered level of a CEP55 polypeptide (or mRNA encoding a CEP55 polypeptide), an altered level of an CDCA5 polypeptide (or mRNA encoding an CDCA5 polypeptide), an altered level of an KRT2 polypeptide (or mRNA encoding an KRT2 polypeptide), an altered level of a ALOX12 polypeptide (or mRNA encoding a ALOX12 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a ACSL1 polypeptide (or mRNA encoding a ACSL1 polypeptide), and/or an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), in a cancer cells of a ma
  • Example 4 cSCC RNA analysis This analysis looked at the differential expression levels of genes to determine a molecular signature between metastatic and non-metastatic samples, with a total of 128 samples from 125 subjects (3 subjects provided 2 samples each). These samples represent a subset of samples analyzed in Example 3. The results in this Example re-present and expand on at least some of the results provided in other Examples.
  • Figure 14A shows the differential gene expression of the 128 samples studied. The genes included are predictive of outcome including metastasis and survival. Differences were seen between metastatic and non-metastatic tumors across these genes of interest.
  • Table 13 shows the patients’ demographics and clinical characteristics of the metastatic (PMet) group compared to non-metastatic (PNoMet) group. There was no significant difference in terms of sex and immunosuppressant use between the two groups.
  • Table 14 shows the tumor characteristic by metastatic (Met) group compared to non- metastatic (No Met) group. There was no significant difference in terms of age at biopsy and tumor stage between the two groups. T able 13.
  • Cross-validation was used to choose the optimal ⁇ in the LASSO regression and after ⁇ was fixed the genes were chosen from the model fit. Further, due to the cross-validation variations, 100 times cross-validation was used, and every time the genes that were selected were stored in a matrix. Among the 100 times selections, if the genes have been chosen 50 times or above, then the genes were considered predictive of the metastasis.
  • the AUC area under ROC curve
  • Figure 14B Three was used as the optimal cut-off to predict metastasis – i.e., patients who had this risk score 3 or above were considered as having metastasis, patients who had this risk score 2 or below were considered as not having metastasis.
  • the sensitivity, specificity and overall accuracy for this cut-off was 84.1%, 77.4%, and 79.7%. T able 16.
  • an altered level of a FN1 polypeptide (or mRNA encoding a FN1 polypeptide), an altered level of an MGAM polypeptide (or mRNA encoding an MGAM polypeptide), an altered level of an CYP2U1 polypeptide (or mRNA encoding an CYP2U1 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide), an altered level of a EVPL polypeptide (or mRNA encoding a EVPL polypeptide), an altered level of a TRPM1 polypeptide (or mRNA encoding a TRPM1 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level
  • an altered level of a NQO1 polypeptide (or mRNA encoding a NQO1 polypeptide), an altered level of an ZNF750 polypeptide (or mRNA encoding an ZNF750 polypeptide), an altered level of an CDC6 polypeptide (or mRNA encoding an CDC6 polypeptide), an altered level of a CDCA5 polypeptide (or mRNA encoding a CDCA5 polypeptide), an altered level of a ALDH3A2 polypeptide (or mRNA encoding a ALDH3A2 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a ALDH1A1 polypeptide (or mRNA encoding a ALDH1A1 polypeptide), an altered level of a ALOX12 polypeptide (or mRNA encoding a ALOX12 polypeptide), and/or an altered level of a TSGA10
  • Example 5 Predicting Survival of a cSCC Patient A tissue sample containing one or more cSCC cells is obtained from a human having cSCC. The obtained sample is examined for the presence or absence of an altered level of a BIRC5 polypeptide (or mRNA encoding a BIRC5 polypeptide), an altered level of a MELK polypeptide (or mRNA encoding a MELK polypeptide), an altered level of an IFNE polypeptide (or mRNA encoding an IFNE polypeptide), an altered level of a HMGCS1 polypeptide (or mRNA encoding a HMGCS1 polypeptide), an altered level of an ANK2 polypeptide (or mRNA encoding an ANK2 polypeptide), an altered level of a LAMA2 Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide (or mRNA encoding a LAMA2 polypeptide), an altered level of a CYP2U1 poly
  • an altered level of a BIRC5 polypeptide (or mRNA encoding a BIRC5 polypeptide), an altered level of a MELK polypeptide (or mRNA encoding a MELK polypeptide), an altered level of an IFNE polypeptide (or mRNA encoding an IFNE polypeptide), an altered level of a HMGCS1 polypeptide (or mRNA encoding a HMGCS1 polypeptide), an altered level of an ANK2 polypeptide (or mRNA encoding an ANK2 polypeptide), an altered level of a LAMA2 polypeptide (or mRNA encoding a LAMA2 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a Attorney Docket No.07039-2153WO1 / 2022-168 CYP2U1 polypeptide), an altered level of a FAM13C polypeptide (or mRNA encoding a Attorney Docket No
  • the sample lacks an altered level of a BIRC5 polypeptide (or mRNA encoding a BIRC5 polypeptide), an altered level of a MELK polypeptide (or mRNA encoding a MELK polypeptide), an altered level of an IFNE polypeptide (or mRNA encoding an IFNE polypeptide), an altered level of a HMGCS1 polypeptide (or mRNA encoding a HMGCS1 polypeptide), an altered level of an ANK2 polypeptide (or mRNA encoding an ANK2 polypeptide), an altered level of a LAMA2 polypeptide (or mRNA encoding a LAMA2 Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a FAM13C polypeptide (or mRNA encoding a F
  • Example 6 Predicting cSCC Metastasis A tissue sample containing one or more cSCC cells is obtained from a human having cSCC. The obtained sample is examined for the presence or absence of an altered level of a CSAG1 polypeptide (or mRNA encoding a CSAG1 polypeptide), an altered level of an UBE2C polypeptide (or mRNA encoding an UBE2C polypeptide), an altered level of an Attorney Docket No.07039-2153WO1 / 2022-168 ANKRD1 polypeptide (or mRNA encoding an ANKRD1 polypeptide), an altered level of a CSMD3 polypeptide (or mRNA encoding a CSMD3 polypeptide), an altered level of a TOP2A polypeptide (or mRNA encoding a TOP2A polypeptide), an altered level of a TPX2 polypeptide (or mRNA encoding a TPX2 polypeptide), an altered level of a
  • an altered level of a CSAG1 polypeptide (or mRNA encoding a CSAG1 polypeptide), an altered level of an UBE2C polypeptide (or mRNA encoding an UBE2C polypeptide), an altered level of an ANKRD1 polypeptide (or mRNA encoding an ANKRD1 polypeptide), an altered level of a CSMD3 polypeptide (or mRNA encoding a CSMD3 polypeptide), an altered level of a TOP2A polypeptide (or mRNA encoding a TOP2A polypeptide), an altered level of a TPX2 polypeptide (or mRNA encoding a TPX2 polypeptide), an altered level of a KSR2 polypeptide (or mRNA encoding a KSR2 polypeptide), an altered level of a CSMD2 polypeptide (or mRNA encoding a CSMD2 polypeptide), an altered level of a M
  • sample lacks an altered level of a CSAG1 polypeptide (or mRNA encoding a CSAG1 polypeptide), an altered level of an UBE2C polypeptide (or mRNA encoding an UBE2C polypeptide), an altered level of an ANKRD1 polypeptide (or mRNA encoding an ANKRD1 polypeptide), an altered level of a CSMD3 polypeptide (or mRNA encoding a CSMD3 polypeptide), an altered level of a TOP2A polypeptide (or mRNA encoding a TOP2A polypeptide), an altered level of a TPX2 polypeptide (or mRNA encoding a TPX2 polypeptide), an altered level of a KSR2 polypeptide (or mRNA encoding a KSR2 polypeptide), an altered level of a CSMD2 polypeptide (or mRNA encoding a CSMD2 polypeptide), an altered level of a MMP20 poly
  • Example 7 Treating cSCC A tissue sample containing one or more cSCC cells is obtained from a human having cSCC. The obtained sample is examined for the presence or absence of an altered level of a BIRC5 polypeptide (or mRNA encoding a BIRC5 polypeptide), an altered level of a MELK polypeptide (or mRNA encoding a MELK polypeptide), an altered level of an IFNE polypeptide (or mRNA encoding an IFNE polypeptide), an altered level of a HMGCS1 polypeptide (or mRNA encoding a HMGCS1 polypeptide), an altered level of an ANK2 polypeptide (or mRNA encoding an ANK2 polypeptide), an altered level of a LAMA2 polypeptide (or mRNA encoding a LAMA2 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level
  • an altered level of a BIRC5 polypeptide (or mRNA encoding a BIRC5 polypeptide), an altered level of a MELK polypeptide (or mRNA encoding a MELK polypeptide), an altered level of an IFNE polypeptide (or mRNA encoding an IFNE polypeptide), an altered level of a HMGCS1 polypeptide (or mRNA encoding a HMGCS1 polypeptide), an altered level of an ANK2 polypeptide (or mRNA encoding an ANK2 polypeptide), an altered level of a LAMA2 polypeptide (or mRNA encoding a LAMA2 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a FAM13C polypeptide (or mRNA encoding a FAM13C polypeptide), an altered level of a COL25
  • Example 8 Treating cSCC A tissue sample containing one or more cSCC cells is obtained from a human having cSCC.
  • the obtained sample is examined for the presence or absence of an altered level of a BIRC5 polypeptide (or mRNA encoding a BIRC5 polypeptide), an altered level of a MELK polypeptide (or mRNA encoding a MELK polypeptide), an altered level of an IFNE polypeptide (or mRNA encoding an IFNE polypeptide), an altered level of a HMGCS1 polypeptide (or mRNA encoding a HMGCS1 polypeptide), an altered level of an ANK2 polypeptide (or mRNA encoding an ANK2 polypeptide), an altered level of a LAMA2 polypeptide (or mRNA encoding a LAMA2 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a FAM13C Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide (or m
  • the sample lacks an increased level of an altered level of a BIRC5 polypeptide (or mRNA encoding a BIRC5 polypeptide), an altered level of a MELK polypeptide (or mRNA encoding a MELK polypeptide), an altered level of an IFNE polypeptide (or mRNA encoding an IFNE polypeptide), an altered level of a HMGCS1 polypeptide (or mRNA encoding a HMGCS1 polypeptide), an altered level of an ANK2 polypeptide (or mRNA encoding an ANK2 polypeptide), an altered level of a LAMA2 polypeptide (or mRNA encoding a LAMA2 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a FAM13C polypeptide (or mRNA encoding a FAM13C polypeptide), an altered level of a COL
  • Example 9 Treating cSCC A tissue sample containing one or more cSCC cells is obtained from a human having cSCC.
  • the obtained sample is examined for the presence or absence of an altered level of a Attorney Docket No.07039-2153WO1 / 2022-168 CSAG1 polypeptide (or mRNA encoding a CSAG1 polypeptide), an altered level of an UBE2C polypeptide (or mRNA encoding an UBE2C polypeptide), an altered level of an ANKRD1 polypeptide (or mRNA encoding an ANKRD1 polypeptide), an altered level of a CSMD3 polypeptide (or mRNA encoding a CSMD3 polypeptide), an altered level of a TOP2A polypeptide (or mRNA encoding a TOP2A polypeptide), an altered level of a TPX2 polypeptide (or mRNA encoding a TPX2 polypeptide), an altered level of a KSR2 polypeptide (or mRNA encoding a KSR2 polypeptide), an altered level of a CSMD2 polypeptide (or
  • an altered level of a CSAG1 polypeptide (or mRNA encoding a CSAG1 polypeptide), an altered level of an UBE2C polypeptide (or mRNA encoding an UBE2C polypeptide), an altered level of an ANKRD1 polypeptide (or mRNA encoding an ANKRD1 polypeptide), an altered level of a CSMD3 polypeptide (or mRNA encoding a CSMD3 polypeptide), an altered level of a TOP2A polypeptide (or mRNA encoding a TOP2A polypeptide), an altered level of a TPX2 polypeptide (or mRNA encoding a TPX2 polypeptide), an altered level of a KSR2 polypeptide (or mRNA encoding a KSR2 polypeptide), an altered level of a CSMD2 polypeptide (or mRNA encoding a CSMD2 polypeptide), an altered level of a M
  • Example 10 Treating cSCC A tissue sample containing one or more cSCC cells is obtained from a human having cSCC.
  • the obtained sample is examined for the presence or absence of an altered level of a CSAG1 polypeptide (or mRNA encoding a CSAG1 polypeptide), an altered level of an UBE2C polypeptide (or mRNA encoding an UBE2C polypeptide), an altered level of an ANKRD1 polypeptide (or mRNA encoding an ANKRD1 polypeptide), an altered level of a CSMD3 polypeptide (or mRNA encoding a CSMD3 polypeptide), an altered level of a TOP2A polypeptide (or mRNA encoding a TOP2A polypeptide), an altered level of a TPX2 polypeptide (or mRNA encoding a TPX2 polypeptide), an altered level of a KSR2 polypeptide (or mRNA encoding a KSR2 polypeptide), an altered level of a CSMD2 polypeptide (or mRNA encoding a CSMD2 polypeptide), an altered level
  • sample lacks an increased level of an altered level of a CSAG1 polypeptide (or mRNA encoding a CSAG1 polypeptide), an altered level of an UBE2C polypeptide (or mRNA encoding an UBE2C polypeptide), an altered level of an ANKRD1 polypeptide (or mRNA encoding an ANKRD1 polypeptide), an altered level of a CSMD3 polypeptide (or mRNA encoding a CSMD3 polypeptide), an altered level of a TOP2A polypeptide (or mRNA encoding a TOP2A polypeptide), an altered level of a TPX2 polypeptide (or mRNA encoding a TPX2 polypeptide), an altered level of a KSR2 polypeptide (or mRNA encoding a KSR2 polypeptide), an altered level of a CSMD2 polypeptide (or mRNA encoding a CSMD2 polypeptide), an altered level of a

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Pathology (AREA)
  • Analytical Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Physics & Mathematics (AREA)
  • Urology & Nephrology (AREA)
  • Genetics & Genomics (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Biochemistry (AREA)
  • Biomedical Technology (AREA)
  • Oncology (AREA)
  • General Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Cell Biology (AREA)
  • Hospice & Palliative Care (AREA)
  • Biophysics (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

This document relates to methods and materials for assessing and/or treating mammals (e.g., humans) having cutaneous squamous cell carcinoma (cSCC). For example, methods and materials that can be used to identify a mammal (e.g., a human) having a cSCC as being likely to experience a higher survival rate are provided. For example, methods and materials that can be used to determine whether or not a cSCC is likely to metastasize (e.g., likely to metastasize to one or more lymph nodes) are provided. This document also relates to methods and materials for treating a mammal (e.g., a human) having a cSCC where the treatment is selected based, at least in part, on whether or not the cSCC is likely to metastasize.

Description

Attorney Docket No.07039-2153WO1 / 2022-168 METHODS AND MATERIALS FOR ASSESSING AND TREATING CUTANEOUS SQUAMOUS CELL CARCINOMA CROSS REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Patent Application Serial No.63/423,254, filed on November 7, 2022. The disclosure of the prior application is considered part of, and is incorporated by reference in, the disclosure of this application. TECHNICAL FIELD This document relates to methods and materials for assessing and/or treating mammals (e.g., humans) having cutaneous squamous cell carcinoma (cSCC). For example, methods and materials provided herein can be used to identify a mammal (e.g., a human) having a cSCC as being likely to experience a prolonged survival from cSCC. For example, methods and materials provided herein can be used to determine whether or not a cSCC is likely to metastasize (e.g., likely to metastasize to one or more lymph nodes). This document also provides methods and materials for treating a mammal (e.g., a human) having a cSCC where the treatment is selected based, at least in part, on the predicted survival of the mammal and/or whether or not the cSCC is likely to metastasize. BACKGROUND INFORMATION Non-melanoma skin cancers (NMSC), most of which are basal cell carcinoma (BCC) and cSCC, are the most common cancer in humans, and the fifth most costly (Guy et al., Am. J. Prev. Med., 48(2):183-187 (2015); Rogers et al., JAMA Dermatol., 151(10):1081-1086 (2015); and Housman et al., J. Am. Acad. Dermatol., 48(3):425-429 (2003)). In some cases, cSCC can be cured with surgery, but metastasis occurs in up to 5% of patients, and metastatic cSCC carries a poor 5-year survival of only 25-35% (Karia et al., J. Am. Acad. Dermatol.,68(6):957-966 (2013)). SUMMARY This document provides methods and materials for assessing and/or treating cSCC. In some cases, this document provides methods and materials for determining whether or not a Attorney Docket No.07039-2153WO1 / 2022-168 mammal (e.g., a human) having a cSCC is likely to experience a prolonged survival from cSCC and/or whether the cSCC is likely to metastasize (e.g., likely to metastasize to one or more lymph nodes). For example, a sample (e.g., a tissue sample containing one or more cSCC cells) obtained from a mammal having a cSCC can be assessed to determine if the mammal is likely to experience a prolonged survival from cSCC and/or whether the cSCC is likely to metastasize (e.g., likely to metastasize to one or more lymph nodes) based, at least in part, on the molecular signature of the cSCC. For example, a sample (e.g., a tissue sample containing one or more cSCC cells) obtained from a mammal having a cSCC can be assessed for the presence or absence of altered levels (e.g., increased levels or decreased levels) of one or more (e.g., one, two, three, four, five, six, seven, or more) polypeptides (or mRNA encoding such polypeptides) to determine whether or not that mammal is likely to experience prolonged survival from cSCC (e.g., prolonged survival from the time of cSCC diagnosis) and/or whether that cSCC is likely to metastasize. This document also provides methods and materials for treating a mammal (e.g., a human) having a cSCC where the treatment is selected based, at least in part, on the predicted survival of the mammal and/or whether or not the cSCC is likely to metastasize. For example, a mammal (e.g., a human) having a cSCC can be administered one or more cancer treatments that are selected based, at least in part, on the molecular signature of the cSCC. As demonstrated herein, the presence of an altered level of a baculoviral IAP repeat- containing protein 5 (BIRC5) polypeptide (or mRNA encoding a BIRC5 polypeptide), an altered level of a maternal embryonic leucine zipper kinase (MELK) polypeptide (or mRNA encoding a MELK polypeptide), an altered level of an interferon epsilon (IFNE) polypeptide (or mRNA encoding an IFNE polypeptide), an altered level of a hydroxymethylglutaryl-CoA synthase, cytoplasmic (HMGCS1) polypeptide (or mRNA encoding a HMGCS1 polypeptide), an altered level of an ankyrin-2 (ANK2) polypeptide (or mRNA encoding an ANK2 polypeptide), an altered level of a laminin subunit alpha-2 (LAMA2) polypeptide (or mRNA encoding a LAMA2 polypeptide), an altered level of a cytochrome P4502U1 (CYP2U1) polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a family with sequence similarity 13 member C (FAM13C) polypeptide (or mRNA encoding a FAM13C polypeptide), an altered level of a collagen alpha-1 (XXV) chain (COL25A1) Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide (or mRNA encoding a COL25A1 polypeptide), an altered level of a thyroglobulin (TG) polypeptide (or mRNA encoding a TG polypeptide), and/or an altered level of a protocadherin Fat 4 (FAT4) polypeptide (or mRNA encoding a FAT4 polypeptide) in cSCC cells of a mammal having a cSCC can be used to identify that mammal as being likely to experience a prolonged survival from cSCC. Also as demonstrated herein, the presence of an altered level of a chondrosarcoma-associated gene 1 (CSAG1) polypeptide (or mRNA encoding a CSAG1 polypeptide), an altered level of an ubiquitin-conjugating enzyme E2 C (UBE2C) polypeptide (or mRNA encoding an UBE2C polypeptide), an altered level of an ankyrin repeat domain-containing protein 1 (ANKRD1) polypeptide (or mRNA encoding an ANKRD1 polypeptide), an altered level of a CUB and sushi domain-containing protein 3 (CSMD3) polypeptide (or mRNA encoding a CSMD3 polypeptide), an altered level of a topoisomerase 2-alpha (TOP2A) polypeptide (or mRNA encoding a TOP2A polypeptide), an altered level of a targeting protein for Xklp2 (TPX2) polypeptide (or mRNA encoding a TPX2 polypeptide), an altered level of a kinase suppressor of Ras 2 (KSR2) polypeptide (or mRNA encoding a KSR2 polypeptide), an altered level of a CUB and sushi domain- containing protein 2 (CSMD2) polypeptide (or mRNA encoding a CSMD2 polypeptide), an altered level of a matrix metalloproteinase-20 preproprotein (MMP20) polypeptide (or mRNA encoding a MMP20 polypeptide), an altered level of a neuroendocrine convertase 1 (PCSK1) polypeptide (or mRNA encoding a PCSK1 polypeptide), an altered level of a transmembrane protein 150B (TMEM150B) polypeptide (or mRNA encoding a TMEM150B polypeptide), an altered level of an acyl-CoA synthetase long chain family member 1 (ACSL1) polypeptide (or mRNA encoding an ACSL1 polypeptide), an altered level of a testis-specific gene 10 (TSGA10) polypeptide (or mRNA encoding a TSGA10 polypeptide), an altered level of a proto-oncogene c-Kit (KIT) polypeptide (or mRNA encoding a KIT polypeptide), an altered level of a ral guanine nucleotide dissociation stimulator-like 3 (RGL3) polypeptide (or mRNA encoding a RGL3 polypeptide), and/or an altered level of a 85/88 kDa calcium-independent phospholipase A2 (PLA2G6) polypeptide (or mRNA encoding a PLA2G6 polypeptide) in cSCC cells of a mammal having a cSCC can be used to identify that cSCC as being likely to metastasize to one or more lymph nodes. Attorney Docket No.07039-2153WO1 / 2022-168 Also as demonstrated herein, the presence of an altered level of a zinc finger protein 750 (ZNF750) polypeptide (or mRNA encoding a ZNF750 polypeptide), an altered level of a cell division cycle-associated 5 (CDCA5) polypeptide (or mRNA encoding a CDCA5 polypeptide), an altered level of a C-X-C motif chemokine ligand 8 (CXCL8) polypeptide (or mRNA encoding a CXCL8 polypeptide), an altered level of a protein regulator of cytokinesis 1 (PRC1) polypeptide (or mRNA encoding a PRC1 polypeptide), an altered level of a keratin 2 (KRT2) polypeptide (or mRNA encoding a KRT2 polypeptide), an altered level of an arachidonate 12-lipoxygenase, 12S type (ALOX12) polypeptide (or mRNA encoding an ALOX12 polypeptide), an altered level of an aldehyde dehydrogenase 3 family member A2 (ALDH3A2) polypeptide (or mRNA encoding an ALDH3A2 polypeptide), an altered level of a dystrophin (DMD) polypeptide (or mRNA encoding a DMD polypeptide), an altered level of an ACSL1 polypeptide (or mRNA encoding an ACSL1 polypeptide), an altered level of a cytochrome P450 family 4 subfamily F member 3 (CYP4F3) polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a calcium binding and coiled-coil domain 1 (CALCOCO1) polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a caspase 14 (CASP14) polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a centrosomal protein 55 (CEP55) polypeptide (or mRNA encoding a CEP55 polypeptide), an altered level of a NAD(P)H quinone dehydrogenase 1 (NQO1) polypeptide (or mRNA encoding a NQO1 polypeptide), an altered level of an aldehyde dehydrogenase 1 family member A1 (ALDH1A1) polypeptide (or mRNA encoding an ALDH1A1 polypeptide), an altered level of a cell division cycle 6 (CDC6) polypeptide (or mRNA encoding a CDC6 polypeptide), and/or an altered level of a testis specific 10 (TSGA10) polypeptide (or mRNA encoding a TSGA10 polypeptide) in cSCC cells of a mammal having a cSCC can be used to identify that mammal as being likely to experience a prolonged survival (e.g., overall survival or disease-free survival) from cSCC. For example, the presence of an altered level of an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide), an altered level of a CDCA5 polypeptide (or mRNA encoding a CDCA5 polypeptide), an altered level of a CXCL8 polypeptide (or mRNA encoding a CXCL8 polypeptide), an altered level of a PRC1 polypeptide (or mRNA encoding a PRC1 polypeptide), an altered level of a KRT2 polypeptide (or mRNA encoding Attorney Docket No.07039-2153WO1 / 2022-168 a KRT2 polypeptide), an altered level of an ALOX12 polypeptide (or mRNA encoding an ALOX12 polypeptide), an altered level of an ALDH3A2 polypeptide (or mRNA encoding an ALDH3A2 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of an ACSL1 polypeptide (or mRNA encoding an ACSL1 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a CEP55 polypeptide (or mRNA encoding a CEP55 polypeptide) in cSCC cells of a mammal having a cSCC can be used to identify that mammal as being likely to experience a prolonged survival (e.g., overall survival or disease-free survival) from cSCC. For example, the presence of an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide), an altered level of a CDCA5 polypeptide (or mRNA encoding a CDCA5 polypeptide), an altered level of an ALOX12 polypeptide (or mRNA encoding a ALOX12 polypeptide), an altered level of an ALDH3A2 polypeptide (or mRNA encoding an ALDH3A2 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a NQO1 polypeptide (or mRNA encoding a NQO1 polypeptide), an altered level of an ALDH1A1 polypeptide (or mRNA encoding an ALDH1A1 polypeptide), an altered level of a cell division cycle 6 (CDC6) polypeptide (or mRNA encoding a CDC6 polypeptide), and/or an altered level of a TSGA10 polypeptide (or mRNA encoding a TSGA10 polypeptide) in cSCC cells of a mammal having a cSCC can be used to identify that mammal as being likely to experience a prolonged survival (e.g., overall survival or disease-free survival) from cSCC. Also as demonstrated herein, the presence of an altered level of a KIT proto-oncogene (KIT) polypeptide (or mRNA encoding a KIT polypeptide), an altered level of a cytochrome P450 family 2 subfamily U member 1 (CYP2U1) polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a Attorney Docket No.07039-2153WO1 / 2022-168 CASP14 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of a fibronectin 1 (FN1) polypeptide (or mRNA encoding a FN1 polypeptide), an altered level of a maltase-glucoamylase (MGAM) polypeptide (or mRNA encoding a MGAM polypeptide), an altered level of a cytochrome P450 family 2 subfamily E member 1 (CYP2E1) polypeptide (or mRNA encoding a CYP2E1 polypeptide), an altered level of an envoplakin (EVPL) polypeptide (or mRNA encoding an EVPL polypeptide), an altered level of a fatty acid synthase (FASN) polypeptide (or mRNA encoding a FASN polypeptide), an altered level of a transient receptor potential cation channel subfamily M member 1 (TRPM1) polypeptide (or mRNA encoding a TRPM1 polypeptide), an altered level of a cytochrome P450 family 4 subfamily F member 22 (CYP4F22) polypeptide (or mRNA encoding a CYP4F22 polypeptide), an altered level of a ceramide synthase 3 (CERS3) polypeptide (or mRNA encoding a CERS3 polypeptide), an altered level of an aldehyde oxidase 1 (AOX1) polypeptide (or mRNA encoding an AOX1 polypeptide), and/or an altered level of a phospholipase A2 receptor 1 (PLA2R1) polypeptide (or mRNA encoding a PLA2R1 polypeptide) in cSCC cells of a mammal having a cSCC can be used to identify that cSCC as being likely to metastasize to one or more lymph nodes. For example, , the presence of an altered level of KIT polypeptide (or mRNA encoding a KIT polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of a FN1 polypeptide (or mRNA encoding a FN1 polypeptide), an altered level of a MGAM polypeptide (or mRNA encoding a MGAM polypeptide), an altered level of a CYP2E1 polypeptide (or mRNA encoding a CYP2E1 polypeptide), an altered level of an EVPL polypeptide (or mRNA encoding an EVPL polypeptide), an altered level of a FASN polypeptide (or mRNA encoding a FASN polypeptide), an altered level of an AOX1 polypeptide (or mRNA encoding an AOX1 polypeptide), an altered level of a PLA2R1 polypeptide (or mRNA encoding a PLA2R1 polypeptide), and/or an altered level of Attorney Docket No.07039-2153WO1 / 2022-168 a TRPM1 polypeptide (or mRNA encoding a TRPM1 polypeptide) in cSCC cells of a mammal having a cSCC can be used to identify that cSCC as being likely to metastasize to one or more lymph nodes. For example, the presence of an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of a FN1 polypeptide (or mRNA encoding a FN1 polypeptide), an altered level of a MGAM polypeptide (or mRNA encoding a MGAM polypeptide), an altered level of an EVPL polypeptide (or mRNA encoding an EVPL polypeptide), an altered level of an AOX1 polypeptide (or mRNA encoding an AOX1 polypeptide), an altered level of a PLA2R1 polypeptide (or mRNA encoding a PLA2R1 polypeptide), an altered level of a TRPM1 polypeptide (or mRNA encoding a TRPM1 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a CYP4F22 polypeptide (or mRNA encoding a CYP4F22 polypeptide), and/or an altered level of a CERS3 polypeptide (or mRNA encoding a CERS3 polypeptide) in cSCC cells of a mammal having a cSCC can be used to identify that cSCC as being likely to metastasize to one or more lymph nodes. Having the ability to predict survival of a cSCC patient and to identify whether a cSCC is likely to metastasize (e.g., likely to metastasize to one or more lymph nodes) as described herein (e.g., based, at least in part, on the molecular signature of the cSCC) provides a unique and unrealized opportunity to provide an individualized approach for selecting cancer therapies based on the risk of the patient, thereby providing cost-effective care with better outcomes in this identified patient population. For example, a mammal having a high-risk cSCC (e.g., a cSCC that is identified as being likely to metastasize as described herein) can be selected for adjuvant therapies, increased screening, and/or participation in clinical trials. For example, a mammal having a low-risk cSCC (e.g., a cSCC that is identified as not being likely to metastasize as described herein) can forgo unnecessary treatments (e.g., sentinel lymph node biopsies (SLNBs) and complete lymph node dissections (CLNDs)) and be spared from the risks and complications associated with some treatments (e.g., SLNBs and CLNDs). Attorney Docket No.07039-2153WO1 / 2022-168 In general, one aspect of this document features methods for assessing a mammal having a cSCC. The methods can include, or consist essentially of, (a) determining if a sample from a mammal having a cSCC contains the presence or absence of at least one of (1) an altered level of a BIRC5 polypeptide or mRNA encoding a BIRC5 polypeptide, (2) an altered level of a MELK polypeptide or mRNA encoding a MELK polypeptide, (3) an altered level of an IFNE polypeptide or mRNA encoding an IFNE polypeptide, (4) an altered level of a HMGCS1 polypeptide or mRNA encoding a HMGCS1 polypeptide, (5) an altered level of an ANK2 polypeptide or mRNA encoding an ANK2 polypeptide, (6) an altered level of a LAMA2 polypeptide or mRNA encoding a LAMA2 polypeptide, (7) an altered level of a CYP2U1 polypeptide or mRNA encoding a CYP2U1 polypeptide, (8) an altered level of a FAM13C polypeptide or mRNA encoding a FAM13C polypeptide, (9) an altered level of a COL25A1 polypeptide or mRNA encoding a COL25A1 polypeptide, (10) an altered level of a TG polypeptide or mRNA encoding a TG polypeptide, and (11) an altered level of a FAT4 polypeptide or mRNA encoding a FAT4 polypeptide; (b) classifying the mammal as being likely to experience a higher survival rate if the presence is determined; and (c) classifying the mammal as not being likely to experience a higher survival rate if the absence of each of (1)-(11) is determined. The mammal can be a human. The presence or absence of the altered level of the BIRC5 polypeptide can be determined. The presence or absence of the altered level of the MELK polypeptide can be determined. The presence or absence of the altered level of the IFNE polypeptide can be determined. The presence or absence of the altered level of the HMGCS1 polypeptide can be determined. The presence or absence of the altered level of the ANK2 polypeptide can be determined. The presence or absence of the altered level of the LAMA2 polypeptide can be determined. The presence or absence of the altered level of the CYP2U1 polypeptide can be determined. The presence or absence of the altered level of the FAM13C polypeptide can be determined. The presence or absence of the altered level of the COL25A1 polypeptide can be determined. The presence or absence of the altered level of the TG polypeptide can be determined. The presence or absence of the altered level of the FAT4 polypeptide can be determined. The sample can be a tissue sample comprising a cSCC cell. Attorney Docket No.07039-2153WO1 / 2022-168 In another aspect, this document features methods for assessing a mammal having a cSCC. The methods can include, or consist essentially of, (a) determining if a sample from a mammal having a cSCC contains the presence or absence of at least one of (1) an altered level of a CSAG1 polypeptide or mRNA encoding a CSAG1 polypeptide, (2) an altered level of an UBE2C polypeptide or mRNA encoding an UBE2C polypeptide, (3) an altered level of an ANKRD1 polypeptide or mRNA encoding an ANKRD1 polypeptide, (4) an altered level of a CSMD3 polypeptide or mRNA encoding a CSMD3 polypeptide, (5) an altered level of a TOP2A polypeptide or mRNA encoding a TOP2A polypeptide, (6) an altered level of a TPX2 polypeptide or mRNA encoding a TPX2 polypeptide, (7) an altered level of a KSR2 polypeptide or mRNA encoding a KSR2 polypeptide, (8) an altered level of a CSMD2 polypeptide or mRNA encoding a CSMD2 polypeptide, (9) an altered level of a MMP20 polypeptide or mRNA encoding a MMP20 polypeptide, (10) an altered level of a PCSK1 polypeptide or mRNA encoding a PCSK1 polypeptide, (11) an altered level of a TMEM150B polypeptide or mRNA encoding a TMEM150B polypeptide, (12) an altered level of an ACSL1 polypeptide or mRNA encoding an ACSL1 polypeptide, (13) an altered level of a TSGA10 polypeptide or mRNA encoding a TSGA10 polypeptide, (14) an altered level of a KIT polypeptide or mRNA encoding a KIT polypeptide, (15) an altered level of a RGL3 polypeptide or mRNA encoding a RGL3 polypeptide, and (16) an altered level of a PLA2G6 polypeptide or mRNA encoding a PLA2G6 polypeptide; (b) classifying the cSCC as being likely to metastasize if the presence is determined; and (c) classifying the cSCC as not being likely to metastasize if the absence of each of (1)-(16) is determined. The mammal can be a human. The presence or absence of the altered level of the CSAG1 polypeptide can be determined. The presence or absence of the altered level of the UBE2C polypeptide can be determined. The presence or absence of the altered level of the ANKRD1 polypeptide can be determined. The presence or absence of the altered level of the CSMD3 polypeptide can be determined. The presence or absence of the altered level of the TOP2A polypeptide can be determined. The presence or absence of the altered level of the TPX2 polypeptide can be determined. The presence or absence of the altered level of the KSR2 polypeptide can be determined. The presence or absence of the altered level of the CSMD2 polypeptide is determined. The presence or absence of the altered level of the MMP20 polypeptide is Attorney Docket No.07039-2153WO1 / 2022-168 determined. The presence or absence of the altered level of the PCSK1 polypeptide can be determined. The presence or absence of the altered level of the TMEM150B polypeptide can be determined. The presence or absence of the altered level of the ACSL1 polypeptide can be determined. The presence or absence of the altered level of the TSGA10 polypeptide can be determined. The presence or absence of the altered level of the KIT polypeptide can be determined. The presence or absence of the altered level of the RGL3 polypeptide can be determined. The presence or absence of the altered level of the PLA2G6 polypeptide can be determined. The sample can be a tissue sample comprising a cSCC cell. In another aspect, this document features methods for selecting a treatment for a mammal having a cSCC. The methods can include, or consist essentially of, (a) determining that a sample from a mammal having a cSCC contains: the absence of (a-1) an altered level of a BIRC5 polypeptide or mRNA encoding a BIRC5 polypeptide, (a-2) an altered level of a MELK polypeptide or mRNA encoding a MELK polypeptide, (a-3) an altered level of an IFNE polypeptide or mRNA encoding an IFNE polypeptide, (a-4) an altered level of a HMGCS1 polypeptide or mRNA encoding a HMGCS1 polypeptide, (a-5) an altered level of an ANK2 polypeptide or mRNA encoding an ANK2 polypeptide, (a-6) an altered level of a LAMA2 polypeptide or mRNA encoding a LAMA2 polypeptide, (a-7) an altered level of a CYP2U1 polypeptide or mRNA encoding a CYP2U1 polypeptide, (a-8) an altered level of a FAM13C polypeptide or mRNA encoding a FAM13C polypeptide, (a-9) an altered level of a COL25A1 polypeptide or mRNA encoding a COL25A1 polypeptide, (a-10) an altered level of a TG polypeptide or mRNA encoding a TG polypeptide, and (a-11) an altered level of a FAT4 polypeptide or mRNA encoding a FAT4 polypeptide; or the presence of at least one of (a-12) an altered level of a CSAG1 polypeptide or mRNA encoding a CSAG1 polypeptide, (a-13) an altered level of an UBE2C polypeptide or mRNA encoding an UBE2C polypeptide, (a-14) an altered level of an ANKRD1 polypeptide or mRNA encoding an ANKRD1 polypeptide, (a-15) an altered level of a CSMD3 polypeptide or mRNA encoding a CSMD3 polypeptide, (a-16) an altered level of a TOP2A polypeptide or mRNA encoding a TOP2A polypeptide, (a-17) an altered level of a TPX2 polypeptide or mRNA encoding a TPX2 polypeptide, (a-18) an altered level of a KSR2 polypeptide or mRNA encoding a KSR2 polypeptide, (a-19) an altered level of a CSMD2 polypeptide or mRNA encoding a CSMD2 Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide, (a-20) an altered level of a MMP20 polypeptide or mRNA encoding a MMP20 polypeptide, (a-21) an altered level of a PCSK1 polypeptide or mRNA encoding a PCSK1 polypeptide, (a-22) an altered level of a TMEM150B polypeptide or mRNA encoding a TMEM150B polypeptide, (a-23) an altered level of an ACSL1 polypeptide or mRNA encoding an ACSL1 polypeptide, (a-24) an altered level of a TSGA10 polypeptide or mRNA encoding a TSGA10 polypeptide, (a-25) an altered level of a KIT polypeptide or mRNA encoding a KIT polypeptide, (a-26) an altered level of a RGL3 polypeptide or mRNA encoding a RGL3 polypeptide, and (a-27) an altered level of a PLA2G6 polypeptide or mRNA encoding a PLA2G6 polypeptide; and (b) selecting the mammal for surgery to remove the cSCC and to receive an adjuvant therapy. The mammal can be a human. The adjuvant therapy can include radiation therapy. The adjuvant therapy can include administering an anti-cancer drug to the mammal. The anti-cancer can becemiplimab-rwlc, nivolumab, ipilimumab, pembrolizumab, talimogene laherparepvec, cetuximab, capecitabine, carboplatin, or fluorouracil (5-FU). In another aspect, this document features methods for selecting a treatment for a mammal having a cSCC. The methods can include, or consist essentially of, (a) determining that a sample from a mammal having a cSCC contains: the presence of at least one of (a-1) an altered level of a BIRC5 polypeptide or mRNA encoding a BIRC5 polypeptide, (a-2) an altered level of a MELK polypeptide or mRNA encoding a MELK polypeptide, (a-3) an altered level of an IFNE polypeptide or mRNA encoding an IFNE polypeptide, (a-4) an altered level of a HMGCS1 polypeptide or mRNA encoding a HMGCS1 polypeptide, (a-5) an altered level of an ANK2 polypeptide or mRNA encoding an ANK2 polypeptide, (a-6) an altered level of a LAMA2 polypeptide or mRNA encoding a LAMA2 polypeptide, (a-7) an altered level of a CYP2U1 polypeptide or mRNA encoding a CYP2U1 polypeptide, (a-8) an altered level of a FAM13C polypeptide or mRNA encoding a FAM13C polypeptide, (a-9) an altered level of a COL25A1 polypeptide or mRNA encoding a COL25A1 polypeptide, (a-10) an altered level of a TG polypeptide or mRNA encoding a TG polypeptide, and (a-11) an altered level of a FAT4 polypeptide or mRNA encoding a FAT4 polypeptide; or the absence of (a-12) an altered level of a CSAG1 polypeptide or mRNA encoding a CSAG1 polypeptide, (a-13) an altered level of an UBE2C polypeptide or mRNA encoding an UBE2C polypeptide, Attorney Docket No.07039-2153WO1 / 2022-168 (a-14) an altered level of an ANKRD1 polypeptide or mRNA encoding an ANKRD1 polypeptide, (a-15) an altered level of a CSMD3 polypeptide or mRNA encoding a CSMD3 polypeptide, (a-16) an altered level of a TOP2A polypeptide or mRNA encoding a TOP2A polypeptide, (a-17) an altered level of a TPX2 polypeptide or mRNA encoding a TPX2 polypeptide, (a-18) an altered level of a KSR2 polypeptide or mRNA encoding a KSR2 polypeptide, (a-19) an altered level of a CSMD2 polypeptide or mRNA encoding a CSMD2 polypeptide, (a-20) an altered level of a MMP20 polypeptide or mRNA encoding a MMP20 polypeptide, (a-21) an altered level of a PCSK1 polypeptide or mRNA encoding a PCSK1 polypeptide, (a-22) an altered level of a TMEM150B polypeptide or mRNA encoding a TMEM150B polypeptide, (a-23) an altered level of an ACSL1 polypeptide or mRNA encoding an ACSL1 polypeptide, (a-24) an altered level of a TSGA10 polypeptide or mRNA encoding a TSGA10 polypeptide, (a-25) an altered level of a KIT polypeptide or mRNA encoding a KIT polypeptide, (a-26) an altered level of a RGL3 polypeptide or mRNA encoding a RGL3 polypeptide, and (a-27) an altered level of a PLA2G6 polypeptide or mRNA encoding a PLA2G6 polypeptide; and (b) selecting the mammal for surgery to remove the cSCC in the absence of an adjuvant therapy. The mammal can be a human. The adjuvant therapy can include radiation therapy. The adjuvant therapy can include administering an anti-cancer drug to the mammal. The anti-cancer can becemiplimab-rwlc, nivolumab, ipilimumab, pembrolizumab, talimogene laherparepvec, cetuximab, capecitabine, carboplatin, or 5-FU. In another aspect, this document features methods for treating a mammal having a cSCC. The methods can include, or consist essentially of, (a) determining that a sample from a mammal having a cSCC contains: the absence of (a-1) an altered level of a BIRC5 polypeptide or mRNA encoding a BIRC5 polypeptide, (a-2) an altered level of a MELK polypeptide or mRNA encoding a MELK polypeptide, (a-3) an altered level of an IFNE polypeptide or mRNA encoding an IFNE polypeptide, (a-4) an altered level of a HMGCS1 polypeptide or mRNA encoding a HMGCS1 polypeptide, (a-5) an altered level of an ANK2 polypeptide or mRNA encoding an ANK2 polypeptide, (a-6) an altered level of a LAMA2 polypeptide or mRNA encoding a LAMA2 polypeptide, (a-7) an altered level of a CYP2U1 polypeptide or mRNA encoding a CYP2U1 polypeptide, (a-8) an altered level of a FAM13C Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide or mRNA encoding a FAM13C polypeptide, (a-9) an altered level of a COL25A1 polypeptide or mRNA encoding a COL25A1 polypeptide, (a-10) an altered level of a TG polypeptide or mRNA encoding a TG polypeptide, and (a-11) an altered level of a FAT4 polypeptide or mRNA encoding a FAT4 polypeptide; or the presence of at least one of (a-12) an altered level of a CSAG1 polypeptide or mRNA encoding a CSAG1 polypeptide, (a-13) an altered level of an UBE2C polypeptide or mRNA encoding an UBE2C polypeptide, (a-14) an altered level of an ANKRD1 polypeptide or mRNA encoding an ANKRD1 polypeptide, (a-15) an altered level of a CSMD3 polypeptide or mRNA encoding a CSMD3 polypeptide, (a-16) an altered level of a TOP2A polypeptide or mRNA encoding a TOP2A polypeptide, (a-17) an altered level of a TPX2 polypeptide or mRNA encoding a TPX2 polypeptide, (a-18) an altered level of a KSR2 polypeptide or mRNA encoding a KSR2 polypeptide, (a-19) an altered level of a CSMD2 polypeptide or mRNA encoding a CSMD2 polypeptide, (a-20) an altered level of a MMP20 polypeptide or mRNA encoding a MMP20 polypeptide, (a-21) an altered level of a PCSK1 polypeptide or mRNA encoding a PCSK1 polypeptide, (a-22) an altered level of a TMEM150B polypeptide or mRNA encoding a TMEM150B polypeptide, (a-23) an altered level of an ACSL1 polypeptide or mRNA encoding an ACSL1 polypeptide, (a-24) an altered level of a TSGA10 polypeptide or mRNA encoding a TSGA10 polypeptide, (a-25) an altered level of a KIT polypeptide or mRNA encoding a KIT polypeptide, (a-26) an altered level of a RGL3 polypeptide or mRNA encoding a RGL3 polypeptide, and (a-27) an altered level of a PLA2G6 polypeptide or mRNA encoding a PLA2G6 polypeptide; (b) subjecting the mammal to a surgery to remove the cSCC; and (c) administering an adjuvant therapy to the mammal. The mammal can be a human. The sample can be a tissue sample comprising a cSCC cell. The adjuvant therapy can include radiation therapy. The adjuvant therapy can include administering an anti-cancer drug to the mammal. The anti-cancer can be cemiplimab-rwlc, nivolumab, ipilimumab, pembrolizumab, talimogene laherparepvec, cetuximab, capecitabine, carboplatin, or 5-FU. In another aspect, this document features methods for treating a cSCC. The methods can include, or consist essentially of, subjecting a mammal identified as having a sample comprising (a) or (b) to a surgery to remove the cSCC and administering an adjuvant therapy to the mammal, where (a) comprises the absence of (a-1) an altered level of a BIRC5 Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide or mRNA encoding a BIRC5 polypeptide, (a-2) an altered level of a MELK polypeptide or mRNA encoding a MELK polypeptide, (a-3) an altered level of an IFNE polypeptide or mRNA encoding an IFNE polypeptide, (a-4) an altered level of a HMGCS1 polypeptide or mRNA encoding a HMGCS1 polypeptide, (a-5) an altered level of an ANK2 polypeptide or mRNA encoding an ANK2 polypeptide, (a-6) an altered level of a LAMA2 polypeptide or mRNA encoding a LAMA2 polypeptide, (a-7) an altered level of a CYP2U1 polypeptide or mRNA encoding a CYP2U1 polypeptide, (a-8) an altered level of a FAM13C polypeptide or mRNA encoding a FAM13C polypeptide, (a-9) an altered level of a COL25A1 polypeptide or mRNA encoding a COL25A1 polypeptide, (a-10) an altered level of a TG polypeptide or mRNA encoding a TG polypeptide, and (a-11) an altered level of a FAT4 polypeptide or mRNA encoding a FAT4 polypeptide, and where (b) comprises the presence of at least one of (b-1) an altered level of a CSAG1 polypeptide or mRNA encoding a CSAG1 polypeptide, (b-2) an altered level of an UBE2C polypeptide or mRNA encoding an UBE2C polypeptide, (b-3) an altered level of an ANKRD1 polypeptide or mRNA encoding an ANKRD1 polypeptide, (b-4) an altered level of a CSMD3 polypeptide or mRNA encoding a CSMD3 polypeptide, (b-5) an altered level of a TOP2A polypeptide or mRNA encoding a TOP2A polypeptide, (b-6) an altered level of a TPX2 polypeptide or mRNA encoding a TPX2 polypeptide, (b-7) an altered level of a KSR2 polypeptide or mRNA encoding a KSR2 polypeptide, (b-8) an altered level of a CSMD2 polypeptide or mRNA encoding a CSMD2 polypeptide, (b-9) an altered level of a MMP20 polypeptide or mRNA encoding a MMP20 polypeptide, (b-10) an altered level of a PCSK1 polypeptide or mRNA encoding a PCSK1 polypeptide, (b-11) an altered level of a TMEM150B polypeptide or mRNA encoding a TMEM150B polypeptide, (b-12) an altered level of an ACSL1 polypeptide or mRNA encoding an ACSL1 polypeptide, (b-13) an altered level of a TSGA10 polypeptide or mRNA encoding a TSGA10 polypeptide, (b-14) an altered level of a KIT polypeptide or mRNA encoding a KIT polypeptide, (b-15) an altered level of a RGL3 polypeptide or mRNA encoding a RGL3 polypeptide, and (b-16) an altered level of a PLA2G6 polypeptide or mRNA encoding a PLA2G6 polypeptide. The mammal can be a human. The sample can be a tissue sample comprising a cSCC cell. The adjuvant therapy can include radiation therapy. The adjuvant therapy can include administering an anti-cancer drug Attorney Docket No.07039-2153WO1 / 2022-168 to the mammal. The anti-cancer can be cemiplimab-rwlc, nivolumab, ipilimumab, pembrolizumab, talimogene laherparepvec, cetuximab, capecitabine, carboplatin, or 5-FU. In another aspect, this document features methods for treating a mammal having a cSCC. The methods can include, or consist essentially of, (a) determining if a sample from a mammal having a cSCC comprises: the presence of at least one of (a-1) an altered level of a BIRC5 polypeptide or mRNA encoding a BIRC5 polypeptide, (a-2) an altered level of a MELK polypeptide or mRNA encoding a MELK polypeptide, (a-3) an altered level of an IFNE polypeptide or mRNA encoding an IFNE polypeptide, (a-4) an altered level of a HMGCS1 polypeptide or mRNA encoding a HMGCS1 polypeptide, (a-5) an altered level of an ANK2 polypeptide or mRNA encoding an ANK2 polypeptide, (a-6) an altered level of a LAMA2 polypeptide or mRNA encoding a LAMA2 polypeptide, (a-7) an altered level of a CYP2U1 polypeptide or mRNA encoding a CYP2U1 polypeptide, (a-8) an altered level of a FAM13C polypeptide or mRNA encoding a FAM13C polypeptide, (a-9) an altered level of a COL25A1 polypeptide or mRNA encoding a COL25A1 polypeptide, (a-10) an altered level of a TG polypeptide or mRNA encoding a TG polypeptide, and (a-11) an altered level of a FAT4 polypeptide or mRNA encoding a FAT4 polypeptide; or the absence of (a-12) an altered level of a CSAG1 polypeptide or mRNA encoding a CSAG1 polypeptide, (a-13) an altered level of an UBE2C polypeptide or mRNA encoding an UBE2C polypeptide, (a-14) an altered level of an ANKRD1 polypeptide or mRNA encoding an ANKRD1 polypeptide, (a- 15) an altered level of a CSMD3 polypeptide or mRNA encoding a CSMD3 polypeptide, (a- 16) an altered level of a TOP2A polypeptide or mRNA encoding a TOP2A polypeptide, (a- 17) an altered level of a TPX2 polypeptide or mRNA encoding a TPX2 polypeptide, (a-18) an altered level of a KSR2 polypeptide or mRNA encoding a KSR2 polypeptide, (a-19) an altered level of a CSMD2 polypeptide or mRNA encoding a CSMD2 polypeptide, (a-20) an altered level of a MMP20 polypeptide or mRNA encoding a MMP20 polypeptide, (a-21) an altered level of a PCSK1 polypeptide or mRNA encoding a PCSK1 polypeptide, (a-22) an altered level of a TMEM150B polypeptide or mRNA encoding a TMEM150B polypeptide, (a-23) an altered level of an ACSL1 polypeptide or mRNA encoding an ACSL1 polypeptide, (a-24) an altered level of a TSGA10 polypeptide or mRNA encoding a TSGA10 polypeptide, (a-25) an altered level of a KIT polypeptide or mRNA encoding a KIT polypeptide, (a-26) an Attorney Docket No.07039-2153WO1 / 2022-168 altered level of a RGL3 polypeptide or mRNA encoding a RGL3 polypeptide, and (a-27) an altered level of a PLA2G6 polypeptide or mRNA encoding a PLA2G6 polypeptide; and (b) subjecting the mammal to a surgery to remove the cSCC in the absence of an adjuvant therapy. The mammal can be a human. The sample can be a tissue sample comprising a cSCC cell. The adjuvant therapy can include radiation therapy. The adjuvant therapy can include administering an anti-cancer drug to the mammal. The anti-cancer drug can be cemiplimab- rwlc, nivolumab, ipilimumab, pembrolizumab, talimogene laherparepvec, cetuximab, capecitabine, carboplatin, or 5-FU. In another aspect, this document features methods for treating cSCC. The methods can include, or consist essentially of, subjecting a mammal identified as comprising a sample comprising (a) or (b) to a surgery to remove the cSCC in the absence of an adjuvant therapy, where (a) comprises the presence of at least one of (a-1) an altered level of a BIRC5 polypeptide or mRNA encoding a BIRC5 polypeptide, (a-2) an altered level of a MELK polypeptide or mRNA encoding a MELK polypeptide, (a-3) an altered level of an IFNE polypeptide or mRNA encoding an IFNE polypeptide, (a-4) an altered level of a HMGCS1 polypeptide or mRNA encoding a HMGCS1 polypeptide, (a-5) an altered level of an ANK2 polypeptide or mRNA encoding an ANK2 polypeptide, (a-6) an altered level of a LAMA2 polypeptide or mRNA encoding a LAMA2 polypeptide, (a-7) an altered level of a CYP2U1 polypeptide or mRNA encoding a CYP2U1 polypeptide, (a-8) an altered level of a FAM13C polypeptide or mRNA encoding a FAM13C polypeptide, (a-9) an altered level of a COL25A1 polypeptide or mRNA encoding a COL25A1 polypeptide, (a-10) an altered level of a TG polypeptide or mRNA encoding a TG polypeptide, and (a-11) an altered level of a FAT4 polypeptide or mRNA encoding a FAT4 polypeptide, and where (b) comprises the absence of (b-1) an altered level of a CSAG1 polypeptide or mRNA encoding a CSAG1 polypeptide, (b-2) an altered level of an UBE2C polypeptide or mRNA encoding an UBE2C polypeptide, (b-3) an altered level of an ANKRD1 polypeptide or mRNA encoding an ANKRD1 polypeptide, (b-4) an altered level of a CSMD3 polypeptide or mRNA encoding a CSMD3 polypeptide, (b-5) an altered level of a TOP2A polypeptide or mRNA encoding a TOP2A polypeptide, (b-6) an altered level of a TPX2 polypeptide or mRNA encoding a TPX2 polypeptide, (b-7) an altered level of a KSR2 polypeptide or mRNA encoding a KSR2 Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide, (b-8) an altered level of a CSMD2 polypeptide or mRNA encoding a CSMD2 polypeptide, (b-9) an altered level of a MMP20 polypeptide or mRNA encoding a MMP20 polypeptide, (b-10) an altered level of a PCSK1 polypeptide or mRNA encoding a PCSK1 polypeptide, (b-11) an altered level of a TMEM150B polypeptide or mRNA encoding a TMEM150B polypeptide, (b-12) an altered level of an ACSL1 polypeptide or mRNA encoding an ACSL1 polypeptide, (b-13) an altered level of a TSGA10 polypeptide or mRNA encoding a TSGA10 polypeptide, (b-14) an altered level of a KIT polypeptide or mRNA encoding a KIT polypeptide, (b-15) an altered level of a RGL3 polypeptide or mRNA encoding a RGL3 polypeptide, and (b-16) an altered level of a PLA2G6 polypeptide or mRNA encoding a PLA2G6 polypeptide. The mammal can be a human. The sample can be a tissue sample comprising a cSCC cell. The adjuvant therapy can include radiation therapy. The adjuvant therapy can include administering an anti-cancer drug to the mammal. The anti- cancer drug can be cemiplimab-rwlc, nivolumab, ipilimumab, pembrolizumab, talimogene laherparepvec, cetuximab, capecitabine, carboplatin, or 5-FU. In another aspect, this document features methods for assessing a mammal having a cSCC where the methods can include, or consist essentially of, (a) determining if a sample from the mammal contains the presence or absence of at least one of (1) an altered level of an ACSL1 polypeptide or mRNA encoding an ACSL1 polypeptide, (2) an altered level of an ALDH1A1 polypeptide or mRNA encoding an ALDH1A1 polypeptide, (3) an altered level of an ALDH3A2 polypeptide or mRNA encoding an ALDH3A2 polypeptide, (4) an altered level of an ALOX12 polypeptide or mRNA encoding an ALOX12 polypeptide, (5) an altered level of a CALCOCO1 polypeptide or mRNA encoding an CALCOCO1 polypeptide, (6) an altered level of a CASP14 polypeptide or mRNA encoding an CASP14 polypeptide, (7) an altered level of a CDC6 polypeptide or mRNA encoding an CDC6 polypeptide, (8) an altered level of a CDCA5 polypeptide or mRNA encoding an CDCA5 polypeptide, (9) an altered level of a CEP55 polypeptide or mRNA encoding an CEP55 polypeptide, (10) an altered level of a CXCL8 polypeptide or mRNA encoding an CXCL8 polypeptide, (11) an altered level of a CYP4F3 polypeptide or mRNA encoding an CYP4F3 polypeptide, (12) an altered level of a DMD polypeptide or mRNA encoding an DMD polypeptide, (13) an altered level of a KRT2 polypeptide or mRNA encoding an KRT2 polypeptide, (14) an altered level of a Attorney Docket No.07039-2153WO1 / 2022-168 NQO1 polypeptide or mRNA encoding an NQO1 polypeptide, (15) an altered level of a PRC1 polypeptide or mRNA encoding an PRC1 polypeptide, (16) an altered level of a TSGA10 polypeptide or mRNA encoding an TSGA10 polypeptide, and (17) an altered level of a ZNF750 polypeptide or mRNA encoding an ZNF750 polypeptide; (b) classifying the mammal as being likely to experience a higher survival rate if the presence is determined; and (c) classifying the mammal as not being likely to experience a higher survival rate if the absence of each of (1)-(17) is determined. The mammal can be a human. The presence or absence of the altered level of the ACSL1 polypeptide can be determined. The presence or absence of the altered level of the ALDH1A1 polypeptide can be determined. The presence or absence of the altered level of the ALDH3A2 polypeptide can be determined. The presence or absence of the altered level of the ALOX12 polypeptide can be determined. The presence or absence of the altered level of the CALCOCO1 polypeptide can be determined. The presence or absence of the altered level of the CASP14 polypeptide can be determined. The presence or absence of the altered level of the CDC6 polypeptide can be determined. The presence or absence of the altered level of the CDCA5 polypeptide can be determined. The presence or absence of the altered level of the CEP55 polypeptide can be determined. The presence or absence of the altered level of the CXCL8 polypeptide can be determined. The presence or absence of the altered level of the CYP4F3 polypeptide can be determined. The presence or absence of the altered level of the DMD polypeptide can be determined. The presence or absence of the altered level of the KRT2 polypeptide can be determined. The presence or absence of the altered level of the NQO1 polypeptide can be determined. The presence or absence of the altered level of the PRC1 polypeptide can be determined. The presence or absence of the altered level of the TSGA10 polypeptide can be determined. The presence or absence of the altered level of the ZNF750 polypeptide can be determined. The sample can be a tissue sample including a cSCC cell. In another aspect, this document features methods for assessing a mammal having a cSCC where the methods can include, or consist essentially of, (a) determining if a sample from the mammal contains the presence or absence of at least one of (1) an altered level of an aldehyde oxidase 1 (AOX1) polypeptide or mRNA encoding an AOX1 polypeptide, (2) an altered level of a calcium binding and coiled-coil domain 1 (CALCOCO1) polypeptide or Attorney Docket No.07039-2153WO1 / 2022-168 mRNA encoding an CALCOCO1 polypeptide, (3) an altered level of a caspase 14 (CASP14) polypeptide or mRNA encoding an CASP14 polypeptide, (4) an altered level of a cell division cycle 6 (CDC6) polypeptide or mRNA encoding an CDC6 polypeptide, (5) an altered level of a ceramide synthase 3 (CERS3) polypeptide or mRNA encoding an CERS3 polypeptide, (6) an altered level of a cytochrome P450 family 2 subfamily E member 1 (CYP2E1) polypeptide or mRNA encoding an CYP2E1 polypeptide, (7) an altered level of a cytochrome P450 family 2 subfamily U member 1 (CYP2U1) polypeptide or mRNA encoding an CYP2U1 polypeptide, (8) an altered level of a cytochrome P450 family 4 subfamily F member 22 (CYP4F22) polypeptide or mRNA encoding an CYP4F22 polypeptide, (9) an altered level of a cytochrome P450 family 4 subfamily F member 3 (CYP4F3) polypeptide or mRNA encoding an CYP4F3 polypeptide, (10) an altered level of a dystrophin (DMD) polypeptide or mRNA encoding an DMD polypeptide, (11) an altered level of an envoplakin (EVPL) polypeptide or mRNA encoding an EVPL polypeptide, (12) an altered level of a fatty acid synthase (FASN) polypeptide or mRNA encoding an FASN polypeptide, (13) an altered level of a fibronectin 1 (FN1) polypeptide or mRNA encoding an FN1 polypeptide, (14) an altered level of a KIT proto-oncogene (KIT) polypeptide or mRNA encoding an KIT polypeptide, (15) an altered level of a maltase-glucoamylase (MGAM) polypeptide or mRNA encoding an MGAM polypeptide, (16) an altered level of a phospholipase A2 receptor 1 (PLA2R1) polypeptide or mRNA encoding an PLA2R1 polypeptide, (17) an altered level of a transient receptor potential cation channel subfamily M member 1 (TRPM1) polypeptide or mRNA encoding an TRPM1 polypeptide, and (18) an altered level of a zinc finger protein 750 (ZNF750) polypeptide or mRNA encoding an ZNF750 polypeptide; (b) classifying the cSCC as being likely to metastasize if the presence is determined; and (c) classifying the cSCC as not being likely to metastasize if the absence of each of (1)-(18) is determined. The mammal can be a human. The presence or absence of the altered level of the AOX1 polypeptide can be determined. The presence or absence of the altered level of the CALCOCO1 polypeptide can be determined. The presence or absence of the altered level of the CASP14 polypeptide can be determined. The presence or absence of the altered level of the CDC6 polypeptide can be determined. The presence or absence of the altered level of the CERS3 polypeptide can be determined. The presence or absence of the Attorney Docket No.07039-2153WO1 / 2022-168 altered level of the CYP2E1 polypeptide can be determined. The presence or absence of the altered level of the CYP2U1 polypeptide can be determined. The presence or absence of the altered level of the CYP4F22 polypeptide can be determined. The presence or absence of the altered level of the CYP4F3 polypeptide can be determined. The presence or absence of the altered level of the DMD polypeptide can be determined. The presence or absence of the altered level of the EVPL polypeptide can be determined. The presence or absence of the altered level of the FASN polypeptide can be determined. The presence or absence of the altered level of the FN1 polypeptide can be determined. The presence or absence of the altered level of the KIT polypeptide can be determined. The presence or absence of the altered level of the MGAM polypeptide can be determined. The presence or absence of the altered level of the PLA2R1 polypeptide can be determined. The presence or absence of the altered level of the TRPM1 polypeptide can be determined. The presence or absence of the altered level of the ZNF750 polypeptide can be determined. The sample can be a tissue sample including a cSCC cell. In another aspect, this document features methods for selecting a treatment for a mammal having a cSCC where the methods can include, or consist essentially of, (a) determining that a sample from the mammal contains: the absence of (a-1) an altered level of an ACSL1 polypeptide or mRNA encoding an ACSL1 polypeptide, (a-2) an altered level of an ALDH1A1 polypeptide or mRNA encoding an ALDH1A1 polypeptide, (a-3) an altered level of an ALDH3A2 polypeptide or mRNA encoding an ALDH3A2 polypeptide, (a-4) an altered level of an ALOX12 polypeptide or mRNA encoding an ALOX12 polypeptide, (a-5) an altered level of a CALCOCO1 polypeptide or mRNA encoding a CALCOCO1 polypeptide, (a-6) an altered level of a CASP14 polypeptide or mRNA encoding a CASP14 polypeptide, (a-7) an altered level of a CDC6 polypeptide or mRNA encoding a CDC6 polypeptide, (a-8) an altered level of a CDCA5 polypeptide or mRNA encoding a CDCA5 polypeptide, (a-9) an altered level of a CEP55 polypeptide or mRNA encoding a CEP55 polypeptide, (a-10) an altered level of a CXCL8 polypeptide or mRNA encoding a CXCL8 polypeptide, (a-11) an altered level of a CYP4F3 polypeptide or mRNA encoding a CYP4F3 polypeptide, (a-12) an altered level of a DMD polypeptide or mRNA encoding a DMD polypeptide, (a-13) an altered level of a KRT2 polypeptide or mRNA encoding a KRT2 Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide, (a-14) an altered level of a NQO1 polypeptide or mRNA encoding a NQO1 polypeptide, (a-15) an altered level of a PRC1 polypeptide or mRNA encoding a PRC1 polypeptide, (a-16) an altered level of a TSGA10 polypeptide or mRNA encoding a TSGA10 polypeptide, and (a-17) an altered level of a ZNF750 polypeptide or mRNA encoding a ZNF750 polypeptide; or the presence of at least one of (a-18) an altered level of a CYP2U1 polypeptide or mRNA encoding a CYP2U1 polypeptide, (a-19) an altered level of a CASP14 polypeptide or mRNA encoding a CASP14 polypeptide, (a-20) an altered level of a CDC6 polypeptide or mRNA encoding a CDC6 polypeptide, (a-21) an altered level of a FN1 polypeptide or mRNA encoding a FN1 polypeptide, (a-22) an altered level of a MGAM polypeptide or mRNA encoding a MGAM polypeptide, (a-23) an altered level of an EVPL polypeptide or mRNA encoding an EVPL polypeptide, (a-24) an altered level of an AOX1 polypeptide or mRNA encoding an AOX1 polypeptide, (a-25) an altered level of a PLA2R1 polypeptide or mRNA encoding a PLA2R1 polypeptide, (a-26) an altered level of a TRPM1 polypeptide or mRNA encoding a TRPM1 polypeptide, (a-27) an altered level of a DMD polypeptide or mRNA encoding a DMD polypeptide, (a-28) an altered level of a CYP4F22 polypeptide or mRNA encoding a CYP4F22 polypeptide, (a-29) an altered level of a CERS3 polypeptide or mRNA encoding a CERS3 polypeptide, (a-30) an altered level of a KIT polypeptide or mRNA encoding a KIT polypeptide, (a-31) an altered level of a ZNF750 polypeptide or mRNA encoding a ZNF750 polypeptide, (a-32) an altered level of a CYP4F3 polypeptide or mRNA encoding a CYP4F3 polypeptide, (a-33) an altered level of a CYP4F3 polypeptide or mRNA encoding a CYP4F3 polypeptide, (a-34) an altered level of a CALCOCO1 polypeptide or mRNA encoding a CALCOCO1 polypeptide, (a-27) an altered level of a CYP2E1 polypeptide or mRNA encoding a CYP2E1 polypeptide, and (a-35) an altered level of a FASN polypeptide or mRNA encoding a FASN polypeptide; and (b) selecting the mammal for surgery to remove the cSCC and to receive an adjuvant therapy. The mammal can be a human. The adjuvant therapy can include radiation therapy. The adjuvant therapy can include administering an anti-cancer drug to the mammal. The anti- cancer drug can be cemiplimab-rwlc, nivolumab, ipilimumab, pembrolizumab, talimogene laherparepvec, cetuximab, capecitabine, carboplatin, or 5-FU. Attorney Docket No.07039-2153WO1 / 2022-168 In another aspect, this document features methods for selecting a treatment for a mammal having a cSCC where the methods can include, or consist essentially of, (a) determining that a sample from the mammal contains: the presence of at least one of (a-1) an altered level of an ACSL1 polypeptide or mRNA encoding an ACSL1 polypeptide, (a-2) an altered level of an ALDH1A1 polypeptide or mRNA encoding an ALDH1A1 polypeptide, (a- 3) an altered level of an ALDH3A2 polypeptide or mRNA encoding an ALDH3A2 polypeptide, (a-4) an altered level of an ALOX12 polypeptide or mRNA encoding an ALOX12 polypeptide, (a-5) an altered level of a CALCOCO1 polypeptide or mRNA encoding a CALCOCO1 polypeptide, (a-6) an altered level of a CASP14 polypeptide or mRNA encoding a CASP14 polypeptide, (a-7) an altered level of a CDC6 polypeptide or mRNA encoding a CDC6 polypeptide, (a-8) an altered level of a CDCA5 polypeptide or mRNA encoding a CDCA5 polypeptide, (a-9) an altered level of a CEP55 polypeptide or mRNA encoding a CEP55 polypeptide, (a-10) an altered level of a CXCL8 polypeptide or mRNA encoding a CXCL8 polypeptide, (a-11) an altered level of a CYP4F3 polypeptide or mRNA encoding a CYP4F3 polypeptide, (a-12) an altered level of a DMD polypeptide or mRNA encoding a DMD polypeptide, (a-13) an altered level of a KRT2 polypeptide or mRNA encoding a KRT2 polypeptide, (a-14) an altered level of a NQO1 polypeptide or mRNA encoding a NQO1 polypeptide, (a-15) an altered level of a PRC1 polypeptide or mRNA encoding a PRC1 polypeptide, (a-16) an altered level of a TSGA10 polypeptide or mRNA encoding a TSGA10 polypeptide, and (a-17) an altered level of a ZNF750 polypeptide or mRNA encoding a ZNF750 polypeptide; or the absence of (a-18) an altered level of a CYP2U1 polypeptide or mRNA encoding a CYP2U1 polypeptide, (a-19) an altered level of a CASP14 polypeptide or mRNA encoding a CASP14 polypeptide, (a-20) an altered level of a CDC6 polypeptide or mRNA encoding a CDC6 polypeptide, (a-21) an altered level of a FN1 polypeptide or mRNA encoding a FN1 polypeptide, (a-22) an altered level of a MGAM polypeptide or mRNA encoding a MGAM polypeptide, (a-23) an altered level of an EVPL polypeptide or mRNA encoding an EVPL polypeptide, (a-24) an altered level of an AOX1 polypeptide or mRNA encoding an AOX1 polypeptide, (a-25) an altered level of a PLA2R1 polypeptide or mRNA encoding a PLA2R1 polypeptide, (a-26) an altered level of a TRPM1 polypeptide or mRNA encoding a TRPM1 polypeptide, (a-27) an altered level of a Attorney Docket No.07039-2153WO1 / 2022-168 DMD polypeptide or mRNA encoding a DMD polypeptide, (a-28) an altered level of a CYP4F22 polypeptide or mRNA encoding a CYP4F22 polypeptide, (a-29) an altered level of a CERS3 polypeptide or mRNA encoding a CERS3 polypeptide, (a-30) an altered level of a KIT polypeptide or mRNA encoding a KIT polypeptide, (a-31) an altered level of a ZNF750 polypeptide or mRNA encoding a ZNF750 polypeptide, (a-32) an altered level of a CYP4F3 polypeptide or mRNA encoding a CYP4F3 polypeptide, (a-33) an altered level of a CYP4F3 polypeptide or mRNA encoding a CYP4F3 polypeptide, (a-34) an altered level of a CALCOCO1 polypeptide or mRNA encoding a CALCOCO1 polypeptide, (a-35) an altered level of a CYP2E1 polypeptide or mRNA encoding a CYP2E1 polypeptide, and (a-36) an altered level of a FASN polypeptide or mRNA encoding a FASN polypeptide; and (b) selecting the mammal for surgery to remove the cSCC in the absence of an adjuvant therapy. The mammal can be a human. The adjuvant therapy can include radiation therapy. The adjuvant therapy can include administering an anti-cancer drug to the mammal. The anti- cancer drug can be cemiplimab-rwlc, nivolumab, ipilimumab, pembrolizumab, talimogene laherparepvec, cetuximab, capecitabine, carboplatin, or 5-FU. In another aspect, this document features methods for treating a mammal having a cSCC where the methods can include, or consist essentially of, (a) determining that a sample from the mammal contains: the absence of (a-1) an altered level of an ACSL1 polypeptide or mRNA encoding an ACSL1 polypeptide, (a-2) an altered level of an ALDH1A1 polypeptide or mRNA encoding an ALDH1A1 polypeptide, (a-3) an altered level of an ALDH3A2 polypeptide or mRNA encoding an ALDH3A2 polypeptide, (a-4) an altered level of an ALOX12 polypeptide or mRNA encoding an ALOX12 polypeptide, (a-5) an altered level of a CALCOCO1 polypeptide or mRNA encoding a CALCOCO1 polypeptide, (a-6) an altered level of a CASP14 polypeptide or mRNA encoding a CASP14 polypeptide, (a-7) an altered level of a CDC6 polypeptide or mRNA encoding a CDC6 polypeptide, (a-8) an altered level of a CDCA5 polypeptide or mRNA encoding a CDCA5 polypeptide, (a-9) an altered level of a CEP55 polypeptide or mRNA encoding a CEP55 polypeptide, (a-10) an altered level of a CXCL8 polypeptide or mRNA encoding a CXCL8 polypeptide, (a-11) an altered level of a CYP4F3 polypeptide or mRNA encoding a CYP4F3 polypeptide, (a-12) an altered level of a DMD polypeptide or mRNA encoding a DMD polypeptide, (a-13) an altered level of a KRT2 Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide or mRNA encoding a KRT2 polypeptide, (a-14) an altered level of a NQO1 polypeptide or mRNA encoding a NQO1 polypeptide, (a-15) an altered level of a PRC1 polypeptide or mRNA encoding a PRC1 polypeptide, (a-16) an altered level of a TSGA10 polypeptide or mRNA encoding a TSGA10 polypeptide, and (a-17) an altered level of a ZNF750 polypeptide or mRNA encoding a ZNF750 polypeptide; or the presence of at least one of (a-18) an altered level of a CYP2U1 polypeptide or mRNA encoding a CYP2U1 polypeptide, (a-19) an altered level of a CASP14 polypeptide or mRNA encoding a CASP14 polypeptide, (a-20) an altered level of a CDC6 polypeptide or mRNA encoding a CDC6 polypeptide, (a-21) an altered level of a FN1 polypeptide or mRNA encoding a FN1 polypeptide, (a-22) an altered level of a MGAM polypeptide or mRNA encoding a MGAM polypeptide, (a-23) an altered level of an EVPL polypeptide or mRNA encoding an EVPL polypeptide, (a-24) an altered level of an AOX1 polypeptide or mRNA encoding an AOX1 polypeptide, (a-25) an altered level of a PLA2R1 polypeptide or mRNA encoding a PLA2R1 polypeptide, (a-26) an altered level of a TRPM1 polypeptide or mRNA encoding a TRPM1 polypeptide, (a-27) an altered level of a DMD polypeptide or mRNA encoding a DMD polypeptide, (a-28) an altered level of a CYP4F22 polypeptide or mRNA encoding a CYP4F22 polypeptide, (a-29) an altered level of a CERS3 polypeptide or mRNA encoding a CERS3 polypeptide, (a-30) an altered level of a KIT polypeptide or mRNA encoding a KIT polypeptide, (a-31) an altered level of a ZNF750 polypeptide or mRNA encoding a ZNF750 polypeptide, (a-32) an altered level of a CYP4F3 polypeptide or mRNA encoding a CYP4F3 polypeptide, (a-33) an altered level of a CYP4F3 polypeptide or mRNA encoding a CYP4F3 polypeptide, (a-34) an altered level of a CALCOCO1 polypeptide or mRNA encoding a CALCOCO1 polypeptide, (a-35) an altered level of a CYP2E1 polypeptide or mRNA encoding a CYP2E1 polypeptide, and (a-36) an altered level of a FASN polypeptide or mRNA encoding a FASN polypeptide; (b) subjecting the mammal to a surgery to remove the cSCC; and (c) administering an adjuvant therapy to the mammal. The mammal can be a human. The sample can be a tissue sample including a cSCC cell. The adjuvant therapy can include radiation therapy. The adjuvant therapy can include administering an anti-cancer drug to the mammal. The anti-cancer drug can be cemiplimab-rwlc, nivolumab, ipilimumab, pembrolizumab, talimogene laherparepvec, cetuximab, capecitabine, carboplatin, or 5-FU. Attorney Docket No.07039-2153WO1 / 2022-168 In another aspect, this document features methods for treating a cSCC where the methods can include, or consist essentially of, subjecting a mammal identified as having a sample including (a) or (b) to a surgery to remove the cSCC and administering an adjuvant therapy to the mammal, where the (a) includes the absence of (a-1) an altered level of an ACSL1 polypeptide or mRNA encoding an ACSL1 polypeptide, (a-2) an altered level of an ALDH1A1 polypeptide or mRNA encoding an ALDH1A1 polypeptide, (a-3) an altered level of an ALDH3A2 polypeptide or mRNA encoding an ALDH3A2 polypeptide, (a-4) an altered level of an ALOX12 polypeptide or mRNA encoding an ALOX12 polypeptide, (a-5) an altered level of a CALCOCO1 polypeptide or mRNA encoding a CALCOCO1 polypeptide, (a-6) an altered level of a CASP14 polypeptide or mRNA encoding a CASP14 polypeptide, (a-7) an altered level of a CDC6 polypeptide or mRNA encoding a CDC6 polypeptide, (a-8) an altered level of a CDCA5 polypeptide or mRNA encoding a CDCA5 polypeptide, (a-9) an altered level of a CEP55 polypeptide or mRNA encoding a CEP55 polypeptide, (a-10) an altered level of a CXCL8 polypeptide or mRNA encoding a CXCL8 polypeptide, (a-11) an altered level of a CYP4F3 polypeptide or mRNA encoding a CYP4F3 polypeptide, (a-12) an altered level of a DMD polypeptide or mRNA encoding a DMD polypeptide, (a-13) an altered level of a KRT2 polypeptide or mRNA encoding a KRT2 polypeptide, (a-14) an altered level of a NQO1 polypeptide or mRNA encoding a NQO1 polypeptide, (a-15) an altered level of a PRC1 polypeptide or mRNA encoding a PRC1 polypeptide, (a-16) an altered level of a TSGA10 polypeptide or mRNA encoding a TSGA10 polypeptide, and (a- 17) an altered level of a ZNF750 polypeptide or mRNA encoding a ZNF750 polypeptide, and where the (b) includes the presence of at least one of (b-1) an altered level of a CYP2U1 polypeptide or mRNA encoding a CYP2U1 polypeptide, (b-2) an altered level of a CASP14 polypeptide or mRNA encoding a CASP14 polypeptide, (b-3) an altered level of a CDC6 polypeptide or mRNA encoding a CDC6 polypeptide, (b-4) an altered level of a FN1 polypeptide or mRNA encoding a FN1 polypeptide, (b-5) an altered level of a MGAM polypeptide or mRNA encoding a MGAM polypeptide, (b-6) an altered level of an EVPL polypeptide or mRNA encoding an EVPL polypeptide, (b-7) an altered level of an AOX1 Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide or mRNA encoding an AOX1 polypeptide, (b-8) an altered level of a PLA2R1 polypeptide or mRNA encoding a PLA2R1 polypeptide, (b-9) an altered level of a TRPM1 polypeptide or mRNA encoding a TRPM1 polypeptide, (b-10) an altered level of a DMD polypeptide or mRNA encoding a DMD polypeptide, (b-11) an altered level of a CYP4F22 polypeptide or mRNA encoding a CYP4F22 polypeptide, (b-12) an altered level of a CERS3 polypeptide or mRNA encoding a CERS3 polypeptide, (b-13) an altered level of a KIT polypeptide or mRNA encoding a KIT polypeptide, (b-14) an altered level of a ZNF750 polypeptide or mRNA encoding a ZNF750 polypeptide, (b-15) an altered level of a CYP4F3 polypeptide or mRNA encoding a CYP4F3 polypeptide, (b-16) an altered level of a CYP4F3 polypeptide or mRNA encoding a CYP4F3 polypeptide, (b-17) an altered level of a CALCOCO1 polypeptide or mRNA encoding a CALCOCO1 polypeptide, (b-18) an altered level of a CYP2E1 polypeptide or mRNA encoding a CYP2E1 polypeptide, and (b-19) an altered level of a FASN polypeptide or mRNA encoding a FASN polypeptide. The mammal can be a human. The sample can be a tissue sample including a cSCC cell. The adjuvant therapy can include radiation therapy. The adjuvant therapy can include administering an anti-cancer drug to the mammal. The anti-cancer drug can be cemiplimab-rwlc, nivolumab, ipilimumab, pembrolizumab, talimogene laherparepvec, cetuximab, capecitabine, carboplatin, or 5-FU. In another aspect, this document features methods for treating a mammal having a cSCC where the methods can include, or consist essentially of, (a) determining if a sample from the mammal includes: the presence of at least one of (a-1) an altered level of an ACSL1 polypeptide or mRNA encoding an ACSL1 polypeptide, (a-2) an altered level of an ALDH1A1 polypeptide or mRNA encoding an ALDH1A1 polypeptide, (a-3) an altered level of an ALDH3A2 polypeptide or mRNA encoding an ALDH3A2 polypeptide, (a-4) an altered level of an ALOX12 polypeptide or mRNA encoding an ALOX12 polypeptide, (a-5) an altered level of a CALCOCO1 polypeptide or mRNA encoding a CALCOCO1 polypeptide, (a-6) an altered level of a CASP14 polypeptide or mRNA encoding a CASP14 polypeptide, (a-7) an altered level of a CDC6 polypeptide or mRNA encoding a CDC6 polypeptide, (a-8) an altered level of a CDCA5 polypeptide or mRNA encoding a CDCA5 polypeptide, (a-9) an altered level of a CEP55 polypeptide or mRNA encoding a CEP55 polypeptide, (a-10) an Attorney Docket No.07039-2153WO1 / 2022-168 altered level of a CXCL8 polypeptide or mRNA encoding a CXCL8 polypeptide, (a-11) an altered level of a CYP4F3 polypeptide or mRNA encoding a CYP4F3 polypeptide, (a-12) an altered level of a DMD polypeptide or mRNA encoding a DMD polypeptide, (a-13) an altered level of a KRT2 polypeptide or mRNA encoding a KRT2 polypeptide, (a-14) an altered level of a NQO1 polypeptide or mRNA encoding a NQO1 polypeptide, (a-15) an altered level of a PRC1 polypeptide or mRNA encoding a PRC1 polypeptide, (a-16) an altered level of a TSGA10 polypeptide or mRNA encoding a TSGA10 polypeptide, and (a- 17) an altered level of a ZNF750 polypeptide or mRNA encoding a ZNF750 polypeptide; or the absence of (a-18) an altered level of a CYP2U1 polypeptide or mRNA encoding a CYP2U1 polypeptide, (a-19) an altered level of a CASP14 polypeptide or mRNA encoding a CASP14 polypeptide, (a-20) an altered level of a CDC6 polypeptide or mRNA encoding a CDC6 polypeptide, (a-21) an altered level of a FN1 polypeptide or mRNA encoding a FN1 polypeptide, (a-22) an altered level of a MGAM polypeptide or mRNA encoding a MGAM polypeptide, (a-23) an altered level of an EVPL polypeptide or mRNA encoding an EVPL polypeptide, (a-24) an altered level of an AOX1 polypeptide or mRNA encoding an AOX1 polypeptide, (a-25) an altered level of a PLA2R1 polypeptide or mRNA encoding a PLA2R1 polypeptide, (a-26) an altered level of a TRPM1 polypeptide or mRNA encoding a TRPM1 polypeptide, (a-27) an altered level of a DMD polypeptide or mRNA encoding a DMD polypeptide, (a-28) an altered level of a CYP4F22 polypeptide or mRNA encoding a CYP4F22 polypeptide, (a-29) an altered level of a CERS3 polypeptide or mRNA encoding a CERS3 polypeptide, (a-30) an altered level of a KIT polypeptide or mRNA encoding a KIT polypeptide, (a-31) an altered level of a ZNF750 polypeptide or mRNA encoding a ZNF750 polypeptide, (a-32) an altered level of a CYP4F3 polypeptide or mRNA encoding a CYP4F3 polypeptide, (a-33) an altered level of a CYP4F3 polypeptide or mRNA encoding a CYP4F3 polypeptide, (a-34) an altered level of a CALCOCO1 polypeptide or mRNA encoding a CALCOCO1 polypeptide, (a-27) an altered level of a CYP2E1 polypeptide or mRNA encoding a CYP2E1 polypeptide, and (a-35) an altered level of a FASN polypeptide or mRNA encoding a FASN polypeptide; and (b) subjecting the mammal to a surgery to remove the cSCC in the absence of an adjuvant therapy. The mammal can be a human. The sample can be a tissue sample including a cSCC cell. The adjuvant therapy can include radiation Attorney Docket No.07039-2153WO1 / 2022-168 therapy. The adjuvant therapy can include administering an anti-cancer drug to the mammal. The anti-cancer drug can be cemiplimab-rwlc, nivolumab, ipilimumab, pembrolizumab, talimogene laherparepvec, cetuximab, capecitabine, carboplatin, or 5-FU. In another aspect, this document features methods for treating cSCC where the methods can include, or consist essentially of, subjecting a mammal identified as having a sample including (a) or (b) to a surgery to remove the cSCC in the absence of an adjuvant therapy, where the (a) including the presence of at least one of (a-1) an altered level of an ACSL1 polypeptide or mRNA encoding an ACSL1 polypeptide, (a-2) an altered level of an ALDH1A1 polypeptide or mRNA encoding an ALDH1A1 polypeptide, (a-3) an altered level of an ALDH3A2 polypeptide or mRNA encoding an ALDH3A2 polypeptide, (a-4) an altered level of an ALOX12 polypeptide or mRNA encoding an ALOX12 polypeptide, (a-5) an altered level of a CALCOCO1 polypeptide or mRNA encoding a CALCOCO1 polypeptide, (a-6) an altered level of a CASP14 polypeptide or mRNA encoding a CASP14 polypeptide, (a-7) an altered level of a CDC6 polypeptide or mRNA encoding a CDC6 polypeptide, (a-8) an altered level of a CDCA5 polypeptide or mRNA encoding a CDCA5 polypeptide, (a-9) an altered level of a CEP55 polypeptide or mRNA encoding a CEP55 polypeptide, (a-10) an altered level of a CXCL8 polypeptide or mRNA encoding a CXCL8 polypeptide, (a-11) an altered level of a CYP4F3 polypeptide or mRNA encoding a CYP4F3 polypeptide, (a-12) an altered level of a DMD polypeptide or mRNA encoding a DMD polypeptide, (a-13) an altered level of a KRT2 polypeptide or mRNA encoding a KRT2 polypeptide, (a-14) an altered level of a NQO1 polypeptide or mRNA encoding a NQO1 polypeptide, (a-15) an altered level of a PRC1 polypeptide or mRNA encoding a PRC1 polypeptide, (a-16) an altered level of a TSGA10 polypeptide or mRNA encoding a TSGA10 polypeptide, and (a- 17) an altered level of a ZNF750 polypeptide or mRNA encoding a ZNF750 polypeptide, and where the (b) includes the absence of (b-1) an altered level of a CSAG1 polypeptide or mRNA encoding a CSAG1 polypeptide, (b-2) an altered level of an UBE2C polypeptide or mRNA encoding an UBE2C polypeptide, (b-3) an altered level of an ANKRD1 polypeptide or mRNA encoding an ANKRD1 polypeptide, (b-4) an altered level of a CSMD3 polypeptide or mRNA encoding a CSMD3 polypeptide, (b-5) an altered level of a TOP2A polypeptide or mRNA encoding a TOP2A polypeptide, (b-6) an altered level of a TPX2 polypeptide or Attorney Docket No.07039-2153WO1 / 2022-168 mRNA encoding a TPX2 polypeptide, (b-7) an altered level of a KSR2 polypeptide or mRNA encoding a KSR2 polypeptide, (b-8) an altered level of a CSMD2 polypeptide or mRNA encoding a CSMD2 polypeptide, (b-9) an altered level of a MMP20 polypeptide or mRNA encoding a MMP20 polypeptide, (b-10) an altered level of a PCSK1 polypeptide or mRNA encoding a PCSK1 polypeptide, (b-11) an altered level of a TMEM150B polypeptide or mRNA encoding a TMEM150B polypeptide, (b-12) an altered level of an ACSL1 polypeptide or mRNA encoding an ACSL1 polypeptide, (b-13) an altered level of a TSGA10 polypeptide or mRNA encoding a TSGA10 polypeptide, (b-14) an altered level of a KIT polypeptide or mRNA encoding a KIT polypeptide, (b-15) an altered level of a RGL3 polypeptide or mRNA encoding a RGL3 polypeptide, and (b-16) an altered level of a PLA2G6 polypeptide or mRNA encoding a PLA2G6 polypeptide. The mammal can be a human. The sample can be a tissue sample including a cSCC cell. The adjuvant therapy can include radiation therapy. The adjuvant therapy can include administering an anti-cancer drug to the mammal. The anti-cancer drug can be cemiplimab-rwlc, nivolumab, ipilimumab, pembrolizumab, talimogene laherparepvec, cetuximab, capecitabine, carboplatin, or 5-FU. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Although methods and materials similar or equivalent to those described herein can be used to practice the invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting. The details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will be apparent from the description and drawings, and from the claims. DESCRIPTION OF THE DRAWINGS Figure 1. Heatmap for the correlation coefficients matrix presentation. Figure 2. ROC curve for the risk score. Attorney Docket No.07039-2153WO1 / 2022-168 Figures 3A – 3F. Overall survival KM curves by expression level of HMGCS1 (Figure 3A), BIRC5 (Figure 3B), MELK (Figure 3C), ANK2 (Figure 3D), FCRL5 (Figure 3E), and LAMA2 (Figure 3F). Figures 4A – 4F. Overall survival KM curves by expression level of TG (Figure 4A), CYP2U1 (Figure 4B), FAM13C (Figure 4C), FATA4 (Figure 4D), COL25A1 (Figure 4E), and IFNE (Figure 4F). Figure 5. Overall survival KM curves by risk scores for HMGCS1, ANK2, LAMA2, CYP2U1, FAM13C, COL25A1, BIRC5, MELK, IFNE, TG, and FAT4. Figure 6 shows biomarkers that were differential expressed in a dataset of 186 patients between patients with metastasis (PMet, n=63) and patients without metastasis (PNoMet, n=123). Figures 7A-7B show ROC curves for the risk score of metastasis (Figure 7A) and the risk score of local recurrence or metastasis (Figure 7B). Figures 8A-8D show overall survival KM curves based on analysis with KRT2 (Figure 8A), ALDH3A2 (Figure 8B), ALOX12 (Figure 8C), and DMD (Figure 8D). Figures 9A-9D show overall survival KM curves based on analysis with CXCL8 (Figure 9A), CDCA5 (Figure 9B), ZNF750 (Figure 9C), and PRC1 (Figure 9D). Figures 10A-10B show an overall survival KM curve based on analysis with KRT2, ALDH3A2, ALOX12, DMD, CXCL8, CDCA5, ZNF750, and PRC1 with different risk score groups depicted. Figures 11A-11F show overall survival KM curves based on analysis with KRT2 (Figure 11A), CALCOCO1 (Figure 11B), ALOX12 (Figure 11C), ACSL1 (Figure 11D), CYP4F3 (Figure 11E), and CASP14 (Figure 11F). Figures 12A-12B show overall survival KM curves based on analysis with CEP55 (Figure 12A) and CDCA5 (Figure 13B). Figures 13A-13B show an overall survival KM curve based on analysis with CEP55, CDCA5, KRT2, ALOX12, CYP4F3, CALCOCO1, ACSL1, and CASP14 with different risk score groups depicted. Attorney Docket No.07039-2153WO1 / 2022-168 Figure 14A shows biomarkers that were differentially expressed in another dataset of 128 patients between patients with metastasis (PMet, n=44) and patients without metastasis (PNoMet, n=84). Figure 14B shows an ROC curve for the risk score of metastasis. Figures 15A-15E show overall survival KM curves based on analysis with ALDH1A1 (Figure 15A), DMD (Figure 15B), ALOX12 (Figure 15C), TSGA10 (Figure 15D), and ALDH3A2 (Figure 11E). Figures 16A-16D show overall survival KM curves based on analysis with NQO1 (Figure 16A), ZNF750 (Figure 16B), CDC6 (Figure 16C), and CDCA5 (Figure 16D). Figures 17A-17B show an overall survival KM curve based on analysis with ALDH1A1, DMD, ALOX12, TSGA10, ALDH3A2, NQO1, ZNF750, CDC6, and CDCA5 with different risk score groups depicted. DETAILED DESCRIPTION This document provides methods and materials that can be used to determine whether or not a mammal (e.g., a human) having a cSCC is likely to experience a prolonged survival from cSCC and/or whether the cSCC is likely to metastasize (e.g., likely to metastasize to one or more lymph nodes). For example, a sample (e.g., a tissue sample containing one or more cSCC cells) obtained from a mammal having a cSCC can be assessed for the molecular signature of the cSCC to determine whether or not the mammal is likely to experience prolonged survival from cSCC (e.g., prolonged survival from the time of cSCC diagnosis) and/or whether the cSCC is likely to metastasize. In some cases, the methods and materials provided herein also can include treating a mammal having a cSCC where one or more cancer treatments are selected based, at least in part, on whether the mammal is likely to experience prolonged survival from cSCC (e.g., prolonged survival from the time of cSCC diagnosis) and/or whether or not the cSCC is likely to metastasize. A mammal (e.g., a human) having a cSCC can be assessed to determine whether the mammal is likely to experience prolonged survival from cSCC (e.g., prolonged survival from the time of cSCC diagnosis) and/or to determine whether or not the cSCC is likely to metastasize (e.g., likely to metastasize to one or more lymph nodes) by detecting the Attorney Docket No.07039-2153WO1 / 2022-168 molecular signature of the cSCC. For example, a sample (e.g., a tissue sample containing one or more cSCC cells) obtained from a mammal having a cSCC can be assessed to determine if the mammal is likely to experience prolonged survival from cSCC and/or whether the cSCC is likely to metastasize (e.g., likely to metastasize to one or more lymph nodes) based, at least in part, on the molecular signature of the cSCC. For example, a sample (e.g., a tissue sample containing one or more cSCC cells) obtained from a mammal having a cSCC can be assessed for the presence or absence of an altered level of a BIRC5 polypeptide (or mRNA encoding a BIRC5 polypeptide), an altered level of a MELK polypeptide (or mRNA encoding a MELK polypeptide), an altered level of an IFNE polypeptide (or mRNA encoding an IFNE polypeptide), an altered level of a HMGCS1 polypeptide (or mRNA encoding a HMGCS1 polypeptide), an altered level of an ANK2 polypeptide (or mRNA encoding an ANK2 polypeptide), an altered level of a LAMA2 polypeptide (or mRNA encoding a LAMA2 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a FAM13C polypeptide (or mRNA encoding a FAM13C polypeptide), an altered level of a COL25A1 polypeptide (or mRNA encoding a COL25A1 polypeptide), an altered level of a TG polypeptide (or mRNA encoding a TG polypeptide), an altered level of a FAT4 polypeptide (or mRNA encoding a FAT4 polypeptide), an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide), an altered level of a CDCA5 polypeptide (or mRNA encoding a CDCA5 polypeptide), an altered level of a CXCL8 polypeptide (or mRNA encoding a CXCL8 polypeptide), an altered level of a PRC1 polypeptide (or mRNA encoding a PRC1 polypeptide), an altered level of a KRT2 polypeptide (or mRNA encoding a KRT2 polypeptide), an altered level of an ALOX12 polypeptide (or mRNA encoding an ALOX12 polypeptide), an altered level of an ALDH3A2 polypeptide (or mRNA encoding an ALDH3A2 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of an ACSL1 polypeptide (or mRNA encoding an ACSL1 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a CEP55 polypeptide (or mRNA encoding a CEP55 polypeptide), an altered level of a NQO1 Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide (or mRNA encoding a NQO1 polypeptide), an altered level of an ALDH1A1 polypeptide (or mRNA encoding an ALDH1A1 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), and/or an altered level of a TSGA10 polypeptide (or mRNA encoding a TSGA10 polypeptide) to determine whether that mammal is likely to experience prolonged survival from cSCC. For example, a sample (e.g., a tissue sample containing one or more cSCC cells) obtained from a mammal having a cSCC can be assessed for the presence or absence of an altered level of a CSAG1 polypeptide (or mRNA encoding a CSAG1 polypeptide), an altered level of an UBE2C polypeptide (or mRNA encoding an UBE2C polypeptide), an altered level of an ANKRD1 polypeptide (or mRNA encoding an ANKRD1 polypeptide), an altered level of a CSMD3 polypeptide (or mRNA encoding a CSMD3 polypeptide), an altered level of a TOP2A polypeptide (or mRNA encoding a TOP2A polypeptide), an altered level of a TPX2 polypeptide (or mRNA encoding a TPX2 polypeptide), an altered level of a KSR2 polypeptide (or mRNA encoding a KSR2 polypeptide), an altered level of a CSMD2 polypeptide (or mRNA encoding a CSMD2 polypeptide), an altered level of a MMP20 polypeptide (or mRNA encoding a MMP20 polypeptide), an altered level of a PCSK1 polypeptide (or mRNA encoding a PCSK1 polypeptide), an altered level of a TMEM150B polypeptide (or mRNA encoding a TMEM150B polypeptide), an altered level of an ACSL1 polypeptide (or mRNA encoding an ACSL1 polypeptide), an altered level of a TSGA10 polypeptide (or mRNA encoding a TSGA10 polypeptide), an altered level of a KIT polypeptide (or mRNA encoding a KIT polypeptide), an altered level of a RGL3 polypeptide (or mRNA encoding a RGL3 polypeptide), an altered level of a PLA2G6 polypeptide (or mRNA encoding a PLA2G6 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of a FN1 polypeptide (or mRNA encoding a FN1 polypeptide), an altered level of a MGAM polypeptide (or mRNA encoding a MGAM polypeptide), an altered level of an EVPL polypeptide (or mRNA encoding an EVPL polypeptide), an altered level of an AOX1 polypeptide (or mRNA encoding an AOX1 polypeptide), an altered level of a PLA2R1 polypeptide (or mRNA encoding a PLA2R1 polypeptide), an altered level of a Attorney Docket No.07039-2153WO1 / 2022-168 TRPM1 polypeptide (or mRNA encoding a TRPM1 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a CYP4F22 polypeptide (or mRNA encoding a CYP4F22 polypeptide), an altered level of a CERS3 polypeptide (or mRNA encoding a CERS3 polypeptide), an altered level of a KIT polypeptide (or mRNA encoding a KIT polypeptide), an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a CYP2E1 polypeptide (or mRNA encoding a CYP2E1 polypeptide), and/or an altered level of a FASN polypeptide (or mRNA encoding a FASN polypeptide) to determine whether that cSCC is likely to metastasize to one or more lymph nodes. Any appropriate mammal having a cSCC can be assessed and/or treated as described herein. Examples of mammals that can have cSCC and can be assessed and/or treated as described herein include, without limitation, humans, non-human primates (e.g., monkeys), dogs, cats, horses, cows, pigs, sheep, mice, and rats. In some cases, a human having a cSCC can be assessed and/or treated as described herein. When assessing and/or treating a mammal (e.g., a human) having a cSCC as described herein, the cSCC can be any type of cSCC. For example, a cSCC to be assessed and/or treated as described herein can be any stage of cSCC (e.g., stage 0, stage I, stage II, stage III, or stage IV). In some cases, a cSCC to be assessed and/or treated as described herein can be at any location of a mammal (e.g., a human) being assessed and/or treated as described herein. In some cases, a cSCC can be at a location on a mammal’s body that has been exposed to ultraviolet (UV) radiation. For example, a cSCC can be at a location on a mammal’s body that has had exposure to the sun. For example, a cSCC can be at a location on a mammal’s body that has had exposure to a tanning lamp and/or a tanning bed. Examples of locations on a mammal’s body where a cSCC that can be assessed and/or treated as described herein can occur include, without limitation, chest, back, legs, arms, face, soles of the feet, hands (e.g., palms of the hands), fingernail beds, toe nail beds, head, scalp, face (e.g., lips), periocular and eyelid, ears, neck, abdomen, finger nail matrix, and/or toe nail matrix. Attorney Docket No.07039-2153WO1 / 2022-168 In some cases, the methods described herein can include identifying a mammal (e.g., a human) as having cSCC. Any appropriate method can be used to identify a mammal as having cSCC. For example, physical examination (e.g., to examine the skin to look for signs that may indicate cSCC), imaging techniques (e.g., X-rays, computerized tomography (CT) scanning, and positron emission tomography (PET)), and/or laboratory examination (e.g., of a skin sample obtained by biopsy) can be used to identify a mammal (e.g., a human) as having cSCC. In some cases, a mammal can be identified as having a cSCC without having been subjected to a SLNb. In some cases, a mammal can be identified as having a cSCC and as having a negative SLNb. In some cases, a molecular signature used to determine whether or not mammal having a cSCC is likely to experience prolonged survival from cSCC (e.g., prolonged survival from the time of cSCC diagnosis) and/or whether the cSCC is likely to metastasize (e.g., likely to metastasize to one or more lymph nodes) can include an altered level (e.g., an increased level or a decreased level) of one or more polypeptides (or mRNA encoding such polypeptides). For example, a sample (e.g., a tissue sample containing one or more cSCC cells) obtained from a mammal having a cSCC can be assessed for the presence or absence of an altered level (e.g., an increased level or a decreased level) of one or more polypeptides (or mRNA encoding such polypeptides) to determine whether or not the mammal is likely to experience prolonged survival from cSCC. In some cases, a mammal having a cSCC can be identified as likely to experience prolonged survival from cSCC based, at least in part, on a molecular signature that includes the presence of an altered level of one or more polypeptides (or mRNA encoding such polypeptides) in a sample (e.g., a tissue sample containing one or more cSCC cells) obtained from the mammal. For example, a sample (e.g., a tissue sample containing one or more cSCC cells) obtained from a mammal having a cSCC can be assessed for the presence or absence of an altered level (e.g., an increased level or a decreased level) of one or more polypeptides (or mRNA encoding such polypeptides) to determine whether or not the cSCC is likely to metastasize (e.g., likely to metastasize to one or more lymph nodes). In some cases, a cSCC can be identified as likely to metastasize (e.g., likely to metastasize to one or more lymph nodes) based, at least in part, on a molecular signature that includes the presence of an altered level of one or more polypeptides (or mRNA encoding such Attorney Docket No.07039-2153WO1 / 2022-168 polypeptides) in a sample (e.g., a tissue sample containing one or more cSCC cells) obtained from a mammal having the cSCC. In some cases, an altered level can be an increased level of one or more polypeptides (or mRNA encoding such polypeptides) in a sample (e.g., a tissue sample containing one or more cSCC cells) obtained from a mammal having cSCC. The term “increased level” as used herein with respect to a level of a polypeptide (or mRNA encoding that polypeptide) in a sample refers to any level that is higher than a reference level of the polypeptide (or mRNA). In some cases, an altered level can be a decreased level of a polypeptide (or mRNA encoding that polypeptide) in a sample (e.g., a tissue sample containing one or more cSCC cells) obtained from a mammal having cSCC. The term “decreased level” as used herein with respect to a level of a polypeptide (or mRNA encoding that polypeptide) in a sample refers to any level that is lower than a reference level of the polypeptide (or mRNA). The term “reference level” as used herein with respect to a level of a polypeptide (or mRNA) refers to the level of the polypeptide (or mRNA) typically observed in a control sample. Examples of control samples are samples obtained from mammals that do not have cSCC (e.g., healthy mammals) and samples obtained from mammals having a cSCC at the time of initial diagnosis, where the mammal after treatment experienced metastases-free survival for at least 2 years. In some cases, an altered level (e.g., an increased level or a decreased level) a polypeptide (or mRNA encoding a polypeptide) can be a level that is at least 1-fold different from a reference level of that polypeptide. For example, an increased level of a polypeptide (or mRNA encoding a polypeptide) can be a level that is at least 1-fold greater than a reference level of that polypeptide. For example, a decreased level of a polypeptide (or mRNA encoding a polypeptide) can be a level that is at least 1-fold less than a reference level of that polypeptide. It will be appreciated that levels of polypeptides (or mRNAs) from comparable samples are used when determining whether or not a particular level is an altered level of a polypeptide (or mRNA). For example, when assessing a particular polypeptide in human cSCC cells, a reference level can be the level of that polypeptide expressed in human cSCC cells obtained from a human at the time of initial diagnosis where that human after treatment experienced metastases-free survival of cSCC for at least 2 years. Attorney Docket No.07039-2153WO1 / 2022-168 A sample (e.g., a tissue sample containing one or more cSCC cells) obtained from a mammal (e.g., a human) having a cSCC can be assessed for the presence, absence, or level of any appropriate polypeptides (or mRNAs encoding the polypeptides). Examples of polypeptides that can be present at an altered level in a sample (e.g., a tissue sample containing one or more cSCC cells) obtained from a mammal having a cSCC and likely to experience prolonged survival from cSCC (e.g., prolonged survival from the time of cSCC diagnosis) include, without limitation, CSAG1 polypeptides, UBE2C polypeptides, ANKRD1 polypeptides, CSMD3 polypeptides, TOP2A polypeptides, TPX2 polypeptides, KSR2 polypeptides, CSMD2 polypeptides, MMP20 polypeptides, PCSK1 polypeptides, TMEM150B polypeptides, ACSL1 polypeptides, TSGA10 polypeptides, KIT polypeptides, RGL3 polypeptides, PLA2G6 polypeptides, BIRC5 polypeptides, MELK polypeptides, IFNE polypeptides, HMGCS1 polypeptides, ANK2 polypeptides, LAMA2 polypeptides, CYP2U1 polypeptides, FAM13C polypeptides, COL25A1 polypeptides, TG polypeptides, FAT4 polypeptides, CDC6 polypeptides, CYP2U1 polypeptides, FN1 polypeptides, MGAM polypeptides, CXCL8 polypeptides, ZNF750 polypeptides, CDCA5 polypeptides, CEP55 polypeptides, NQO1 polypeptides, CDCA5 polypeptides, CYP2E1 polypeptides, CYP4F3 polypeptides, CALCOCO1 polypeptides, AOX1 polypeptides, EVPL polypeptides, FASN polypeptides, PLA2R1 polypeptides, CASP14 polypeptides, KRT2 polypeptides, ALOX12 polypeptides, ALDH3A2 polypeptides, DMD polypeptides, TRPM1 polypeptides, CYP4F22 polypeptides, CERS3 polypeptides, and ALDH1A1 polypeptides. Examples of mRNAs that can be present at an altered level in a sample (e.g., a tissue sample containing one or more cSCC cells) obtained from a mammal having a cSCC and likely to experience prolonged survival (e.g., prolonged survival from the time of cSCC diagnosis) from cSCC include, without limitation, mRNAs encoding a CSAG1 polypeptide, mRNAs encoding an UBE2C polypeptide, mRNAs encoding a ANKRD1 polypeptide, mRNAs encoding a CSMD3 polypeptide, mRNAs encoding a TOP2A polypeptide, mRNAs encoding a TPX2 polypeptide, mRNAs encoding a KSR2 polypeptide, mRNAs encoding a CSMD2 polypeptide, mRNAs encoding a MMP20 polypeptide, mRNAs encoding a PCSK1 polypeptide, mRNAs encoding a TMEM150B polypeptide, mRNAs encoding a ACSL1 polypeptide, mRNAs encoding a TSGA10 polypeptide, mRNAs encoding a KIT polypeptide, Attorney Docket No.07039-2153WO1 / 2022-168 mRNAs encoding a RGL3 polypeptide, mRNAs encoding a PLA2G6 polypeptide, mRNAs encoding a BIRC5 polypeptide, mRNAs encoding a MELK polypeptide, mRNAs encoding a IFNE polypeptide, mRNAs encoding a HMGCS1 polypeptide, mRNAs encoding a ANK2 polypeptide, mRNAs encoding a LAMA2 polypeptide, mRNAs encoding a CYP2U1 polypeptide, mRNAs encoding a FAM13C polypeptide, mRNAs encoding a COL25A1 polypeptide, mRNAs encoding a TG polypeptide, mRNAs encoding a FAT4 polypeptide, mRNAs encoding a CDC6 polypeptide, mRNAs encoding a CYP2U1 polypeptide, mRNAs encoding a FN1 polypeptide, mRNAs encoding a MGAM polypeptide, mRNAs encoding a CXCL8 polypeptide, mRNAs encoding a ZNF750 polypeptide, mRNAs encoding a CDCA5 polypeptide, mRNAs encoding a CEP55 polypeptide, mRNAs encoding a NQO1 polypeptide, mRNAs encoding a CDCA5 polypeptide, mRNAs encoding a CYP2E1 polypeptide, mRNAs encoding a CYP4F3 polypeptide, mRNAs encoding a CALCOCO1 polypeptide, mRNAs encoding an AOX1 polypeptide, mRNAs encoding an EVPL polypeptide, mRNAs encoding a FASN polypeptide, mRNAs encoding a PLA2R1 polypeptide, mRNAs encoding a CASP14 polypeptide, mRNAs encoding a KRT2 polypeptide, mRNAs encoding an ALOX12 polypeptide, mRNAs encoding an ALDH3A2 polypeptide, mRNAs encoding a DMD polypeptide, mRNAs encoding a TRPM1 polypeptide, mRNAs encoding a CYP4F22 polypeptide, mRNAs encoding a CERS3 polypeptide, and mRNAs encoding an ALDH1A1 polypeptide. In some cases, a sample (e.g., a tissue sample containing one or more cSCC cells) obtained from a mammal having a cSCC can be assessed for the presence, absence, or level of a BIRC5 polypeptide (or mRNA encoding a BIRC5 polypeptide), a MELK polypeptide (or mRNA encoding a MELK polypeptide), an IFNE polypeptide (or mRNA encoding an IFNE polypeptide), a HMGCS1 polypeptide (or mRNA encoding a HMGCS1 polypeptide), an ANK2 polypeptide (or mRNA encoding an ANK2 polypeptide), a LAMA2 polypeptide (or mRNA encoding a LAMA2 polypeptide), a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), a FAM13C polypeptide (or mRNA encoding a FAM13C polypeptide), a COL25A1 polypeptide (or mRNA encoding a COL25A1 polypeptide), a TG polypeptide (or mRNA encoding a TG polypeptide), and/or a FAT4 polypeptide (or mRNA encoding a FAT4 polypeptide). In some cases, a sample (e.g., a tissue sample containing one or more cSCC Attorney Docket No.07039-2153WO1 / 2022-168 cells) obtained from a mammal having a cSCC can be assessed for the presence, absence, or level of a CSAG1 polypeptide (or mRNA encoding a CSAG1 polypeptide), an UBE2C polypeptide (or mRNA encoding an UBE2C polypeptide), an ANKRD1 polypeptide (or mRNA encoding an ANKRD1 polypeptide), a CSMD3 polypeptide (or mRNA encoding a CSMD3 polypeptide), a TOP2A polypeptide (or mRNA encoding a TOP2A polypeptide), a TPX2 polypeptide (or mRNA encoding a TPX2 polypeptide), a KSR2 polypeptide (or mRNA encoding a KSR2 polypeptide), a CSMD2 polypeptide (or mRNA encoding a CSMD2 polypeptide), a MMP20 polypeptide (or mRNA encoding a MMP20 polypeptide), a PCSK1 polypeptide (or mRNA encoding a PCSK1 polypeptide), a TMEM150B polypeptide (or mRNA encoding a TMEM150B polypeptide), an ACSL1polypeptide (or mRNA encoding an ACSL1polypeptide), a TSGA10 polypeptide (or mRNA encoding a TSGA10 polypeptide), a KIT polypeptide (or mRNA encoding a KIT polypeptide), a RGL3 polypeptide (or mRNA encoding a RGL3 polypeptide), and/or a PLA2G6 polypeptide (or mRNA encoding a PLA2G6 polypeptide). In some cases, a sample (e.g., a tissue sample containing one or more cSCC cells) obtained from a mammal having a cSCC can be assessed for the presence, absence, or level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide), a CDCA5 polypeptide (or mRNA encoding a CDCA5 polypeptide), a CXCL8 polypeptide (or mRNA encoding a CXCL8 polypeptide), a PRC1 polypeptide (or mRNA encoding a PRC1 polypeptide), a KRT2 polypeptide (or mRNA encoding a KRT2 polypeptide), an ALOX12 polypeptide (or mRNA encoding an ALOX12 polypeptide), an ALDH3A2 polypeptide (or mRNA encoding an ALDH3A2 polypeptide), a DMD polypeptide (or mRNA encoding a DMD polypeptide), a ACSL1 polypeptide (or mRNA encoding a ACSL1 polypeptide), a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), a CEP55 polypeptide (or mRNA encoding a CEP55 polypeptide), a NQO1 polypeptide (or mRNA encoding a NQO1 polypeptide), an ALDH1A1 polypeptide (or mRNA encoding an ALDH1A1 polypeptide), a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), and/or a TSGA10 polypeptide (or mRNA encoding a TSGA10 polypeptide). In some cases, a sample (e.g., a tissue sample containing one or more cSCC cells) obtained from a mammal having a cSCC can be assessed Attorney Docket No.07039-2153WO1 / 2022-168 for the presence, absence, or level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), a FN1 polypeptide (or mRNA encoding a FN1 polypeptide), a MGAM polypeptide (or mRNA encoding a MGAM polypeptide), an EVPL polypeptide (or mRNA encoding an EVPL polypeptide), an AOX1 polypeptide (or mRNA encoding an AOX1 polypeptide), a PLA2R1 polypeptide (or mRNA encoding a PLA2R1 polypeptide), a TRPM1 polypeptide (or mRNA encoding a TRPM1 polypeptide), a DMD polypeptide (or mRNA encoding a DMD polypeptide), a CYP4F22 polypeptide (or mRNA encoding a CYP4F22 polypeptide), a CERS3 polypeptide (or mRNA encoding a CERS3 polypeptide), a KIT polypeptide (or mRNA encoding a KIT polypeptide), a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide), a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), a CYP2E1 polypeptide (or mRNA encoding a CYP2E1 polypeptide), and/or a FASN polypeptide (or mRNA encoding a FASN polypeptide). In some cases, a sample (e.g., a tissue sample containing one or more cSCC cells) obtained from a mammal (e.g., a human) having a cSCC is not assessed for the presence, absence, or level of a TP53 polypeptide (and an mRNA encoding a TP53 polypeptide), a CDKN2A polypeptide (and an mRNA encoding a CDKN2A polypeptide), a NOTCH1 polypeptide (and an mRNA encoding a NOTCH1 polypeptide), a FAT1 polypeptide (and an mRNA encoding a FAT1 polypeptide), a HRAS polypeptide (and an mRNA encoding a HRAS polypeptide), and/or a INPP5A polypeptide (and an mRNA encoding a INPP5A polypeptide). In some cases, a sample (e.g., a tissue sample containing one or more cSCC cells) obtained from a mammal (e.g., a human) having a cSCC is not assessed for the presence, absence, or level of a polypeptide (or an mRNA encoding a polypeptide) described in Wysong et al. (J. Am. Acad. Dermatol., 84(2):361-369 (2021)). In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a CSAG1 polypeptide (or an altered level of an mRNA encoding a CSAG1 polypeptide). An example of a CSAG1 polypeptide is, without limitation, the polypeptide set forth in the National Center for Attorney Docket No.07039-2153WO1 / 2022-168 Biotechnology Information (NCBI) databases at, for example, accession no. NP_001096046 (version NP_001096046.2). For example, an altered level of a CSAG1 polypeptide (or an mRNA encoding a CSAG1 polypeptide) can be any level that is at least 1-fold different than a reference level of the CSAG1 polypeptide (or a reference level of an mRNA encoding a CSAG1 polypeptide). In some cases, a reference level of an mRNA encoding a CSAG1 polypeptide in humans can be a level of such mRNA that is about 0.014 fragment per kilobase per million (FPKM) as measured in a RNA-seq technology platform. For example, an increased level of an mRNA encoding a CSAG1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a CSAG1 polypeptide. For example, a decreased level of an mRNA encoding a CSAG1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a CSAG1 polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of an UBE2C polypeptide (or an altered level of an mRNA encoding an UBE2C polypeptide). An example of an UBE2C polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_008950 (version NP_008950.1). For example, an altered level of an UBE2C polypeptide (or an mRNA encoding an UBE2C polypeptide) can be any level that is at least 1-fold different than a reference level of the UBE2C polypeptide (or a reference level of an mRNA encoding an UBE2C polypeptide). In some cases, a reference level of an mRNA encoding an UBE2C polypeptide in humans can be a level of such mRNA that is about 3.234 FPKM as measured in a RNA-seq technology platform. For example, an increased level of an mRNA encoding an UBE2C polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding an UBE2C polypeptide. For example, a decreased level of an mRNA encoding an UBE2C polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at Attorney Docket No.07039-2153WO1 / 2022-168 least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding an UBE2C polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of an ANKRD1 polypeptide (or an altered level of an mRNA encoding an ANKRD1 polypeptide). An example of an ANKRD1 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_055206 (version NP_055206.2). For example, an altered level of an ANKRD1 polypeptide (or an mRNA encoding an ANKRD1 polypeptide) can be any level that is at least 1-fold different than a reference level of the ANKRD1 polypeptide (or a reference level of an mRNA encoding an ANKRD1 polypeptide). In some cases, a reference level of an mRNA encoding an ANKRD1 polypeptide in humans can be a level of such mRNA that is about 0.258 FPKM as measured in a RNA-seq technology platform. For example, an increased level of an mRNA encoding an ANKRD1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding an ANKRD1 polypeptide. For example, a decreased level of an mRNA encoding an ANKRD1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding an ANKRD1 polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a CSMD3 polypeptide (or an altered level of an mRNA encoding a CSMD3 polypeptide). An example of a CSMD3 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_937756 (version NP_937756.1). For example, an altered level of a CSMD3 polypeptide (or an mRNA encoding a CSMD3 polypeptide) can be any level that is at least 1-fold different than a reference level of the CSMD3 polypeptide (or a reference level of an mRNA encoding a CSMD3 polypeptide). In some cases, a reference level of an mRNA encoding a CSMD3 polypeptide in humans can be a level of such mRNA that is about 0.026 FPKM as measured in a RNA-seq technology platform. For example, an increased level of an mRNA encoding a CSMD3 polypeptide can be a level that is at least 1 (e.g., at Attorney Docket No.07039-2153WO1 / 2022-168 least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a CSMD3 polypeptide. For example, a decreased level of an mRNA encoding a CSMD3 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a CSMD3 polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a TOP2A polypeptide (or an altered level of an mRNA encoding a TOP2A polypeptide). An example of a TOP2A polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_001058 (version NP_001058.2). For example, an altered level of a TOP2A polypeptide (or an mRNA encoding a TOP2A polypeptide) can be any level that is at least 1-fold different than a reference level of the TOP2A polypeptide (or a reference level of an mRNA encoding a TOP2A polypeptide). In some cases, a reference level of an mRNA encoding a TOP2A polypeptide in humans can be a level of such mRNA that is about 13.6 FPKM as measured in a RNA-seq technology platform. For example, an increased level of an mRNA encoding a TOP2A polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a TOP2A polypeptide. For example, a decreased level of an mRNA encoding a TOP2A polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a TOP2A polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a TPX2 polypeptide (or an altered level of an mRNA encoding a TPX2 polypeptide). An example of a TPX2 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_036244 (version NP_036244.2). For example, an altered level of a TPX2 polypeptide (or an mRNA encoding a TPX2 polypeptide) can be any level that is at least 1-fold different than a reference level of the TPX2 polypeptide (or a reference level of an mRNA encoding a TPX2 polypeptide). In some cases, a reference level of an mRNA Attorney Docket No.07039-2153WO1 / 2022-168 encoding a TPX2 polypeptide in humans can be a level of such mRNA that is about 5.956 FPKM as measured in a RNA-seq technology platform. For example, an increased level of an mRNA encoding a TPX2 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a TPX2 polypeptide. For example, a decreased level of an mRNA encoding a TPX2 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a TPX2 polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a KSR2 polypeptide (or an altered level of an mRNA encoding a KSR2 polypeptide). An example of a KSR2 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_775869 (version NP_775869.4). For example, an altered level of a KSR2 polypeptide (or an mRNA encoding a KSR2 polypeptide) can be any level that is at least 1-fold different than a reference level of the KSR2 polypeptide (or a reference level of an mRNA encoding a KSR2 polypeptide). In some cases, a reference level of an mRNA encoding a KSR2 polypeptide in humans can be a level of such mRNA that is about 0.022 FPKM as measured in a RNA-seq technology platform. For example, an increased level of an mRNA encoding a KSR2 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a KSR2 polypeptide. For example, a decreased level of an mRNA encoding a KSR2 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a KSR2 polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a CSMD2 polypeptide (or an altered level of an mRNA encoding a CSMD2 polypeptide). An example of a CSMD2 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_001268885 (version NP_001268885.1). For example, an altered level of a CSMD2 polypeptide (or an mRNA encoding a CSMD2 polypeptide) can be any Attorney Docket No.07039-2153WO1 / 2022-168 level that is at least 1-fold different than a reference level of the CSMD2 polypeptide (or a reference level of an mRNA encoding a CSMD2 polypeptide). In some cases, a reference level of an mRNA encoding a CSMD2 polypeptide in humans can be a level of such mRNA that is about 0.347 FPKM as measured in a RNA-seq technology platform. For example, an increased level of an mRNA encoding a CSMD2 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a CSMD2 polypeptide. For example, a decreased level of an mRNA encoding a CSMD2 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a CSMD2 polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a MMP20 polypeptide (or an altered level of an mRNA encoding a MMP20 polypeptide). An example of a MMP20 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_004762 (version NP_004762.2). For example, an altered level of a MMP20 polypeptide (or an mRNA encoding a MMP20 polypeptide) can be any level that is at least 1-fold different than a reference level of the MMP20 polypeptide (or a reference level of an mRNA encoding a MMP20 polypeptide). In some cases, a reference level of an mRNA encoding a MMP20 polypeptide in humans can be a level of such mRNA that is about 0.001 FPKM as measured in a RNA-seq technology platform. For example, an increased level of an mRNA encoding a MMP20 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a MMP20 polypeptide. For example, a decreased level of an mRNA encoding a MMP20 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a MMP20 polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a PCSK1 polypeptide (or an Attorney Docket No.07039-2153WO1 / 2022-168 altered level of an mRNA encoding a PCSK1 polypeptide). An example of a PCSK1 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_001171346 (version NP_001171346.1). For example, an altered level of a PCSK1 polypeptide (or an mRNA encoding a PCSK1 polypeptide) can be any level that is at least 1-fold different than a reference level of the PCSK1 polypeptide (or a reference level of an mRNA encoding a PCSK1 polypeptide). In some cases, a reference level of an mRNA encoding a PCSK1 polypeptide in humans can be a level of such mRNA that is about 0.341 FPKM as measured in a RNA-seq technology platform. For example, an increased level of an mRNA encoding a PCSK1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a PCSK1 polypeptide. For example, a decreased level of an mRNA encoding a PCSK1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a PCSK1 polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a TMEM150B polypeptide (or an altered level of an mRNA encoding a TMEM150B polypeptide). An example of a TMEM150B polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_001078957 (version NP_001078957.1). For example, an altered level of a TMEM150B polypeptide (or an mRNA encoding a TMEM150B polypeptide) can be any level that is at least 1-fold different than a reference level of the TMEM150B polypeptide (or a reference level of an mRNA encoding a TMEM150B polypeptide). In some cases, a reference level of an mRNA encoding a TMEM150B polypeptide in humans can be a level of such mRNA that is about 0.018 FPKM as measured in a RNA-seq technology platform. For example, an increased level of an mRNA encoding a TMEM150B polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a TMEM150B polypeptide. For example, a decreased level of an mRNA encoding a TMEM150B polypeptide can be a level Attorney Docket No.07039-2153WO1 / 2022-168 that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a TMEM150B polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of an ACSL1 polypeptide (or an altered level of an mRNA encoding an ACSL1 polypeptide). An example of an ACSL1 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_001986 (version NP_001986.2). For example, an altered level of an ACSL1 polypeptide (or an mRNA encoding an ACSL1 polypeptide) can be any level that is at least 1-fold different than a reference level of the ACSL1 polypeptide (or a reference level of an mRNA encoding an ACSL1 polypeptide). In some cases, a reference level of an mRNA encoding an ACSL1 polypeptide in humans can be a level of such mRNA that is about 42.066 FPKM as measured in a RNA-seq technology platform. For example, an increased level of an mRNA encoding an ACSL1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding an ACSL1 polypeptide. For example, a decreased level of an mRNA encoding an ACSL1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding an ACSL1 polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a TSGA10 polypeptide (or an altered level of an mRNA encoding a TSGA10 polypeptide). An example of a TSGA10 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_079520 (version NP_079520.1). For example, an altered level of a TSGA10 polypeptide (or an mRNA encoding a TSGA10 polypeptide) can be any level that is at least 1-fold different than a reference level of the TSGA10 polypeptide (or a reference level of an mRNA encoding a TSGA10 polypeptide). In some cases, a reference level of an mRNA encoding a TSGA10 polypeptide in humans can be a level of such mRNA that is about 1.308 FPKM as measured in a RNA-seq technology platform. For example, an Attorney Docket No.07039-2153WO1 / 2022-168 increased level of an mRNA encoding a TSGA10 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a TSGA10 polypeptide. For example, a decreased level of an mRNA encoding a TSGA10 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a TSGA10 polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a KIT polypeptide (or an altered level of an mRNA encoding a KIT polypeptide). An example of a KIT polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_000213 (version NP_000213.1). For example, an altered level of a KIT polypeptide (or an mRNA encoding a KIT polypeptide) can be any level that is at least 1-fold different than a reference level of the KIT polypeptide (or a reference level of an mRNA encoding a KIT polypeptide). In some cases, a reference level of an mRNA encoding a KIT polypeptide in humans can be a level of such mRNA that is about 8.414 FPKM as measured in a RNA- seq technology platform. For example, an increased level of an mRNA encoding a KIT polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a KIT polypeptide. For example, a decreased level of an mRNA encoding a KIT polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a KIT polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a RGL3 polypeptide (or an altered level of an mRNA encoding a RGL3 polypeptide). An example of a RGL3 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_001155088 (version NP_001155088.2). For example, an altered level of a RGL3 polypeptide (or an mRNA encoding a RGL3 polypeptide) can be any level that is at least 1-fold different than a reference level of the RGL3 polypeptide (or a reference Attorney Docket No.07039-2153WO1 / 2022-168 level of an mRNA encoding a RGL3 polypeptide). In some cases, a reference level of an mRNA encoding a RGL3 polypeptide in humans can be a level of such mRNA that is about 0.224 FPKM as measured in a RNA-seq technology platform. For example, an increased level of an mRNA encoding a RGL3 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a RGL3 polypeptide. For example, a decreased level of an mRNA encoding a RGL3 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a RGL3 polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a PLA2G6 polypeptide (or an altered level of an mRNA encoding a PLA2G6 polypeptide). An example of a PLA2G6 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_003551 (version NP_003551.2). For example, an altered level of a PLA2G6 polypeptide (or an mRNA encoding a PLA2G6 polypeptide) can be any level that is at least 1-fold different than a reference level of the PLA2G6 polypeptide (or a reference level of an mRNA encoding a PLA2G6 polypeptide). In some cases, a reference level of an mRNA encoding a PLA2G6 polypeptide in humans can be a level of such mRNA that is about 3.763 FPKM as measured in a RNA-seq technology platform. For example, an increased level of an mRNA encoding a PLA2G6 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a PLA2G6 polypeptide. For example, a decreased level of an mRNA encoding a PLA2G6 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a PLA2G6 polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a BIRC5 polypeptide (or an altered level of an mRNA encoding a BIRC5 polypeptide). An example of a BIRC5 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for Attorney Docket No.07039-2153WO1 / 2022-168 example, accession no. NP_001159 (version NP_001159.2). For example, an altered level of a BIRC5 polypeptide (or an mRNA encoding a BIRC5 polypeptide) can be any level that is at least 1-fold different than a reference level of the BIRC5 polypeptide (or a reference level of an mRNA encoding a BIRC5 polypeptide). In some cases, a reference level of an mRNA encoding a BIRC5 polypeptide in humans can be a level of such mRNA that is about 0.650 FPKM as measured in a RNA-seq technology platform. For example, an increased level of an mRNA encoding a BIRC5 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a BIRC5 polypeptide. For example, a decreased level of an mRNA encoding a BIRC5 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a BIRC5 polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a MELK polypeptide (or an altered level of an mRNA encoding a MELK polypeptide). An example of a MELK polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_055606 (version NP_055606.1). For example, an altered level of a MELK polypeptide (or an mRNA encoding a MELK polypeptide) can be any level that is at least 1-fold different than a reference level of the MELK polypeptide (or a reference level of an mRNA encoding a MELK polypeptide). In some cases, a reference level of an mRNA encoding a MELK polypeptide in humans can be a level of such mRNA that is about 3.543 FPKM as measured in a RNA-seq technology platform. For example, an increased level of an mRNA encoding a MELK polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a MELK polypeptide. For example, a decreased level of an mRNA encoding a MELK polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a MELK polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of an IFNE polypeptide (or an Attorney Docket No.07039-2153WO1 / 2022-168 altered level of an mRNA encoding an IFNE polypeptide). An example of an IFNE polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NM_176891 (version NM_176891.5). For example, an altered level of an IFNE polypeptide (or an mRNA encoding an IFNE polypeptide) can be any level that is at least 1-fold different than a reference level of the IFNE polypeptide (or a reference level of an mRNA encoding an IFNE polypeptide). In some cases, a reference level of an mRNA encoding an IFNE polypeptide in humans can be a level of such mRNA that is about 0.578 FPKM as measured in a RNA-seq technology platform. For example, an increased level of an mRNA encoding an IFNE polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding an IFNE polypeptide. For example, a decreased level of an mRNA encoding an IFNE polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding an IFNE polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a HMGCS1 polypeptide (or an altered level of an mRNA encoding a HMGCS1 polypeptide). An example of a HMGCS1 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_001351117 (version NP_001351117.1). For example, an altered level of a HMGCS1 polypeptide (or an mRNA encoding a HMGCS1 polypeptide) can be any level that is at least 1-fold different than a reference level of the HMGCS1 polypeptide (or a reference level of an mRNA encoding a HMGCS1 polypeptide). In some cases, a reference level of an mRNA encoding a HMGCS1 polypeptide in humans can be a level of such mRNA that is about 34.706 FPKM as measured in a RNA-seq technology platform. For example, an increased level of an mRNA encoding a HMGCS1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a HMGCS1 polypeptide. For example, a decreased level of an mRNA encoding a HMGCS1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, Attorney Docket No.07039-2153WO1 / 2022-168 at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a HMGCS1 polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of an ANK2 polypeptide (or an altered level of an mRNA encoding an ANK2 polypeptide). An example of an ANK2 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_001139 (version NP_001139.3). For example, an altered level of an ANK2 polypeptide (or an mRNA encoding an ANK2 polypeptide) can be any level that is at least 1-fold different than a reference level of the ANK2 polypeptide (or a reference level of an mRNA encoding an ANK2 polypeptide). In some cases, a reference level of an mRNA encoding an ANK2 polypeptide in humans can be a level of such mRNA that is about 12.926 FPKM as measured in a RNA-seq technology platform. For example, an increased level of an mRNA encoding an ANK2 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding an ANK2 polypeptide. For example, a decreased level of an mRNA encoding an ANK2 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding an ANK2 polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a LAMA2 polypeptide (or an altered level of an mRNA encoding a LAMA2 polypeptide). An example of a LAMA2 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_000417 (version NP_000417.3). For example, an altered level of a LAMA2 polypeptide (or an mRNA encoding a LAMA2 polypeptide) can be any level that is at least 1-fold different than a reference level of the LAMA2 polypeptide (or a reference level of an mRNA encoding a LAMA2 polypeptide). In some cases, a reference level of an mRNA encoding a LAMA2 polypeptide in humans can be a level of such mRNA that is about 40.295 FPKM as measured in a RNA-seq technology platform. For example, an increased level of an mRNA encoding a LAMA2 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least Attorney Docket No.07039-2153WO1 / 2022-168 35, or at least 50) fold greater than a reference level of mRNA encoding a LAMA2 polypeptide. For example, a decreased level of an mRNA encoding a LAMA2 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a LAMA2 polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a CYP2U1 polypeptide (or an altered level of an mRNA encoding a CYP2U1 polypeptide). An example of a CYP2U1 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_898898 (version NP_898898.1). For example, an altered level of a CYP2U1 polypeptide (or an mRNA encoding a CYP2U1 polypeptide) can be any level that is at least 1-fold different than a reference level of the CYP2U1 polypeptide (or a reference level of an mRNA encoding a CYP2U1 polypeptide). In some cases, a reference level of an mRNA encoding a CYP2U1 polypeptide in humans can be a level of such mRNA that is about 0.465 FPKM as measured in a RNA-seq technology platform. For example, an increased level of an mRNA encoding a CYP2U1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a CYP2U1 polypeptide. For example, a decreased level of an mRNA encoding a CYP2U1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a CYP2U1 polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a FAM13C polypeptide (or an altered level of an mRNA encoding a FAM13C polypeptide). An example of a FAM13C polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_937858 (version NP_937858.2). For example, an altered level of a FAM13C polypeptide (or an mRNA encoding a FAM13C polypeptide) can be any level that is at least 1-fold different than a reference level of the FAM13C polypeptide (or a reference level of an mRNA encoding a FAM13C polypeptide). In some cases, a reference Attorney Docket No.07039-2153WO1 / 2022-168 level of an mRNA encoding a FAM13C polypeptide in humans can be a level of such mRNA that is about 3.148 FPKM as measured in a RNA-seq technology platform. For example, an increased level of an mRNA encoding a FAM13C polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a FAM13C polypeptide. For example, a decreased level of an mRNA encoding a FAM13C polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a FAM13C polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a COL25A1 polypeptide (or an altered level of an mRNA encoding a COL25A1 polypeptide). An example of a COL25A1 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. NP_942014 (version NP_942014.1). For example, an altered level of a COL25A1 polypeptide (or an mRNA encoding a COL25A1 polypeptide) can be any level that is at least 1-fold different than a reference level of the COL25A1 polypeptide (or a reference level of an mRNA encoding a COL25A1 polypeptide). In some cases, a reference level of an mRNA encoding a COL25A1 polypeptide in humans can be a level of such mRNA that is about 0.294 FPKM as measured in a RNA-seq technology platform. For example, an increased level of an mRNA encoding a COL25A1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a COL25A1 polypeptide. For example, a decreased level of an mRNA encoding a COL25A1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a COL25A1 polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a TG polypeptide (or an altered level of an mRNA encoding a TG polypeptide). An example of a TG polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession Attorney Docket No.07039-2153WO1 / 2022-168 no. XP_006716685 (version XP_006716685.1). For example, an altered level of a TG polypeptide (or an mRNA encoding a TG polypeptide) can be any level that is at least 1-fold different than a reference level of the TG polypeptide (or a reference level of an mRNA encoding a TG polypeptide). In some cases, a reference level of an mRNA encoding a TG polypeptide in humans can be a level of such mRNA that is about 3.017 FPKM as measured in a RNA-seq technology platform. For example, an increased level of an mRNA encoding a TG polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a TG polypeptide. For example, a decreased level of an mRNA encoding a TG polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a TG polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a FAT4 polypeptide (or an altered level of an mRNA encoding a FAT4 polypeptide). An example of a FAT4 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, accession no. XP_047272107 (version XP_047272107.1). For example, an altered level of a FAT4 polypeptide (or an mRNA encoding a FAT4 polypeptide) can be any level that is at least 1-fold different than a reference level of the FAT4 polypeptide (or a reference level of an mRNA encoding a FAT4 polypeptide). In some cases, a reference level of an mRNA encoding a FAT4 polypeptide in humans can be a level of such mRNA that is about 6.658 FPKM as measured in a RNA-seq technology platform. For example, an increased level of an mRNA encoding a FAT4 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a FAT4 polypeptide. For example, a decreased level of an mRNA encoding a FAT4 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a FAT4 polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of an AOX1 polypeptide (or an Attorney Docket No.07039-2153WO1 / 2022-168 altered level of an mRNA encoding an AOX1 polypeptide). An example of an AOX1 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, XP_011509364 (version XP_011509364.1). For example, an altered level of an AOX1 polypeptide (or an mRNA encoding an AOX1 polypeptide) can be any level that is at least 1-fold different than a reference level of the AOX1 polypeptide (or a reference level of an mRNA encoding an AOX1 polypeptide). For example, an increased level of an mRNA encoding an AOX1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding an AOX1 polypeptide. For example, a decreased level of an mRNA encoding an AOX1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding an AOX1 polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a CDC6 polypeptide (or an altered level of an mRNA encoding a CDC6 polypeptide). An example of a CDC6 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, XP_011523844 (version XP_011523844.1). For example, an altered level of a CDC6 polypeptide (or an mRNA encoding a CDC6 polypeptide) can be any level that is at least 1-fold different than a reference level of the CDC6 polypeptide (or a reference level of an mRNA encoding a CDC6 polypeptide). For example, an increased level of an mRNA encoding a CDC6 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a CDC6 polypeptide. For example, a decreased level of an mRNA encoding a CDC6 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a CDC6 polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a FN1 polypeptide (or an altered level of an mRNA encoding a FN1 polypeptide). An example of a FN1 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, Attorney Docket No.07039-2153WO1 / 2022-168 NP_001293058 (version NP_001293058.2). For example, an altered level of a FN1 polypeptide (or an mRNA encoding a FN1 polypeptide) can be any level that is at least 1-fold different than a reference level of the FN1 polypeptide (or a reference level of an mRNA encoding a FN1 polypeptide). For example, an increased level of an mRNA encoding a FN1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a FN1 polypeptide. For example, a decreased level of an mRNA encoding a FN1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a FN1 polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a MGAM polypeptide (or an altered level of an mRNA encoding a MGAM polypeptide). An example of a MGAM polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, XP_011514972 (version XP_011514972.1). For example, an altered level of a MGAM polypeptide (or an mRNA encoding a MGAM polypeptide) can be any level that is at least 1-fold different than a reference level of the MGAM polypeptide (or a reference level of an mRNA encoding a MGAM polypeptide). For example, an increased level of an mRNA encoding a MGAM polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a MGAM polypeptide. For example, a decreased level of an mRNA encoding a MGAM polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a MGAM polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a CYP2E1 polypeptide (or an altered level of an mRNA encoding a CYP2E1 polypeptide). An example of a CYP2E1 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, NP_000764 (version NP_000764.1). For example, an altered level of a CYP2E1 polypeptide (or an mRNA encoding a CYP2E1 polypeptide) can be any level that is at least Attorney Docket No.07039-2153WO1 / 2022-168 1-fold different than a reference level of the CYP2E1 polypeptide (or a reference level of an mRNA encoding a CYP2E1 polypeptide). For example, an increased level of an mRNA encoding a CYP2E1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a CYP2E1 polypeptide. For example, a decreased level of an mRNA encoding a CYP2E1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a CYP2E1 polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a CYP4F3 polypeptide (or an altered level of an mRNA encoding a CYP4F3 polypeptide). An example of a CYP4F3 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, XP_011526316 (version XP_011526316.1). For example, an altered level of a CYP4F3 polypeptide (or an mRNA encoding a CYP4F3 polypeptide) can be any level that is at least 1-fold different than a reference level of the CYP4F3 polypeptide (or a reference level of an mRNA encoding a CYP4F3 polypeptide). For example, an increased level of an mRNA encoding a CYP4F3 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a CYP4F3 polypeptide. For example, a decreased level of an mRNA encoding a CYP4F3 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a CYP4F3 polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a CALCOCO1 polypeptide (or an altered level of an mRNA encoding a CALCOCO1 polypeptide). An example of a CALCOCO1 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, XP_011536903 (version XP_011536903.1). For example, an altered level of a CALCOCO1 polypeptide (or an mRNA encoding a CALCOCO1 polypeptide) can be any level that is at least 1-fold different than a reference level of the CALCOCO1 polypeptide (or a reference level of an mRNA encoding a CALCOCO1 Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide). For example, an increased level of an mRNA encoding a CALCOCO1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a CALCOCO1 polypeptide. For example, a decreased level of an mRNA encoding a CALCOCO1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a CALCOCO1 polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of an EVPL polypeptide (or an altered level of an mRNA encoding an EVPL polypeptide). An example of an EVPL polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, NP_001307676 (version NP_001307676.1). For example, an altered level of an EVPL polypeptide (or an mRNA encoding an EVPL polypeptide) can be any level that is at least 1-fold different than a reference level of the EVPL polypeptide (or a reference level of an mRNA encoding an EVPL polypeptide). For example, an increased level of an mRNA encoding an EVPL polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding an EVPL polypeptide. For example, a decreased level of an mRNA encoding an EVPL polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding an EVPL polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a FASN polypeptide (or an altered level of an mRNA encoding a FASN polypeptide). An example of a FASN polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, XP_011521840 (version XP_011521840.1). For example, an altered level of a FASN polypeptide (or an mRNA encoding a FASN polypeptide) can be any level that is at least 1-fold different than a reference level of the FASN polypeptide (or a reference level of an mRNA encoding a FASN polypeptide). For example, an increased level of an mRNA encoding a FASN polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at Attorney Docket No.07039-2153WO1 / 2022-168 least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a FASN polypeptide. For example, a decreased level of an mRNA encoding a FASN polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a FASN polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a CASP14 polypeptide (or an altered level of an mRNA encoding a CASP14 polypeptide). An example of a CASP14 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, XP_011526163 (version XP_011526163.1). For example, an altered level of a CASP14 polypeptide (or an mRNA encoding a CASP14 polypeptide) can be any level that is at least 1-fold different than a reference level of the CASP14 polypeptide (or a reference level of an mRNA encoding a CASP14 polypeptide). For example, an increased level of an mRNA encoding a CASP14 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a CASP14 polypeptide. For example, a decreased level of an mRNA encoding a CASP14 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a CASP14 polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a ZNF750 polypeptide (or an altered level of an mRNA encoding a ZNF750 polypeptide). An example of a ZNF750 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, NP_078978 (version NP_078978.2). For example, an altered level of a ZNF750 polypeptide (or an mRNA encoding a ZNF750 polypeptide) can be any level that is at least 1- fold different than a reference level of the ZNF750 polypeptide (or a reference level of an mRNA encoding a ZNF750 polypeptide). For example, an increased level of an mRNA encoding a ZNF750 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a ZNF750 polypeptide. For example, a decreased Attorney Docket No.07039-2153WO1 / 2022-168 level of an mRNA encoding a ZNF750 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a ZNF750 polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a TRPM1 polypeptide (or an altered level of an mRNA encoding a TRPM1 polypeptide). An example of a TRPM1 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, XP_054187771 (version XP_054187771.1). For example, an altered level of a TRPM1 polypeptide (or an mRNA encoding a TRPM1 polypeptide) can be any level that is at least 1-fold different than a reference level of the TRPM1 polypeptide (or a reference level of an mRNA encoding a TRPM1 polypeptide). For example, an increased level of an mRNA encoding a TRPM1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a TRPM1 polypeptide. For example, a decreased level of an mRNA encoding a TRPM1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a TRPM1 polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a CDCA5 polypeptide (or an altered level of an mRNA encoding a CDCA5 polypeptide). An example of a CDCA5 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, XP_011543045 (version XP_011543045.1). For example, an altered level of a CDCA5 polypeptide (or an mRNA encoding a CDCA5 polypeptide) can be any level that is at least 1-fold different than a reference level of the CDCA5 polypeptide (or a reference level of an mRNA encoding a CDCA5 polypeptide). For example, an increased level of an mRNA encoding a CDCA5 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a CDCA5 polypeptide. For example, a decreased level of an mRNA encoding a CDCA5 polypeptide can be a level that is at least 1 (e.g., at Attorney Docket No.07039-2153WO1 / 2022-168 least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a CDCA5 polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a CXCL8 polypeptide (or an altered level of an mRNA encoding a CXCL8 polypeptide). An example of a CXCL8 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, NP_000575 (version NP_000575.1). For example, an altered level of a CXCL8 polypeptide (or an mRNA encoding a CXCL8 polypeptide) can be any level that is at least 1- fold different than a reference level of the CXCL8 polypeptide (or a reference level of an mRNA encoding a CXCL8 polypeptide). For example, an increased level of an mRNA encoding a CXCL8 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a CXCL8 polypeptide. For example, a decreased level of an mRNA encoding a CXCL8 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a CXCL8 polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a PRC1 polypeptide (or an altered level of an mRNA encoding a PRC1 polypeptide). An example of a PRC1 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, XP_016878203 (version XP_016878203.1). For example, an altered level of a PRC1 polypeptide (or an mRNA encoding a PRC1 polypeptide) can be any level that is at least 1-fold different than a reference level of the PRC1 polypeptide (or a reference level of an mRNA encoding a PRC1 polypeptide). For example, an increased level of an mRNA encoding a PRC1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a PRC1 polypeptide. For example, a decreased level of an mRNA encoding a PRC1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a PRC1 polypeptide. Attorney Docket No.07039-2153WO1 / 2022-168 In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a KRT2 polypeptide (or an altered level of an mRNA encoding a KRT2 polypeptide). An example of a KRT2 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, NP_000414 (version NP_000414.2). For example, an altered level of a KRT2 polypeptide (or an mRNA encoding a KRT2 polypeptide) can be any level that is at least 1- fold different than a reference level of the KRT2 polypeptide (or a reference level of an mRNA encoding a KRT2 polypeptide). For example, an increased level of an mRNA encoding a KRT2 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a KRT2 polypeptide. For example, a decreased level of an mRNA encoding a KRT2 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a KRT2 polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of an ALOX12 polypeptide (or an altered level of an mRNA encoding an ALOX12 polypeptide). An example of an ALOX12 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, XP_011522082 (version XP_011522082.2). For example, an altered level of an ALOX12 polypeptide (or an mRNA encoding an ALOX12 polypeptide) can be any level that is at least 1-fold different than a reference level of the ALOX12 polypeptide (or a reference level of an mRNA encoding an ALOX12 polypeptide). For example, an increased level of an mRNA encoding an ALOX12 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding an ALOX12 polypeptide. For example, a decreased level of an mRNA encoding an ALOX12 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding an ALOX12 polypeptide. Attorney Docket No.07039-2153WO1 / 2022-168 In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of an ALDH3A2 polypeptide (or an altered level of an mRNA encoding an ALDH3A2 polypeptide). An example of an ALDH3A2 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, XP_024306419 (version XP_024306419.1). For example, an altered level of an ALDH3A2 polypeptide (or an mRNA encoding an ALDH3A2 polypeptide) can be any level that is at least 1-fold different than a reference level of the ALDH3A2 polypeptide (or a reference level of an mRNA encoding an ALDH3A2 polypeptide). For example, an increased level of an mRNA encoding an ALDH3A2 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding an ALDH3A2 polypeptide. For example, a decreased level of an mRNA encoding an ALDH3A2 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding an ALDH3A2 polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a DMD polypeptide (or an altered level of an mRNA encoding a DMD polypeptide). An example of a DMD polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, XP_006724532 (version XP_006724532.1). For example, an altered level of a DMD polypeptide (or an mRNA encoding a DMD polypeptide) can be any level that is at least 1-fold different than a reference level of the DMD polypeptide (or a reference level of an mRNA encoding a DMD polypeptide). For example, an increased level of an mRNA encoding a DMD polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a DMD polypeptide. For example, a decreased level of an mRNA encoding a DMD polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a DMD polypeptide. Attorney Docket No.07039-2153WO1 / 2022-168 In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a CEP55 polypeptide (or an altered level of an mRNA encoding a CEP55 polypeptide). An example of a CEP55 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, XP_016871862 (version XP_016871862.1). For example, an altered level of a CEP55 polypeptide (or an mRNA encoding a CEP55 polypeptide) can be any level that is at least 1-fold different than a reference level of the CEP55 polypeptide (or a reference level of an mRNA encoding a CEP55 polypeptide). For example, an increased level of an mRNA encoding a CEP55 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a CEP55 polypeptide. For example, a decreased level of an mRNA encoding a CEP55 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a CEP55 polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a CYP4F22 polypeptide (or an altered level of an mRNA encoding a CYP4F22 polypeptide). An example of a CYP4F22 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, XP_011525994 (version XP_011525994.1). For example, an altered level of a CYP4F22 polypeptide (or an mRNA encoding a CYP4F22 polypeptide) can be any level that is at least 1-fold different than a reference level of the CYP4F22 polypeptide (or a reference level of an mRNA encoding a CYP4F22 polypeptide). For example, an increased level of an mRNA encoding a CYP4F22 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a CYP4F22 polypeptide. For example, a decreased level of an mRNA encoding a CYP4F22 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a CYP4F22 polypeptide. Attorney Docket No.07039-2153WO1 / 2022-168 In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a CERS3 polypeptide (or an altered level of an mRNA encoding a CERS3 polypeptide). An example of a CERS3 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, XP_011519657 (version XP_011519657.1). For example, an altered level of a CERS3 polypeptide (or an mRNA encoding a CERS3 polypeptide) can be any level that is at least 1-fold different than a reference level of the CERS3 polypeptide (or a reference level of an mRNA encoding a CERS3 polypeptide). For example, an increased level of an mRNA encoding a CERS3 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a CERS3 polypeptide. For example, a decreased level of an mRNA encoding a CERS3 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a CERS3 polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of a NQO1 polypeptide (or an altered level of an mRNA encoding a NQO1 polypeptide). An example of a NQO1 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, NP_000894.1 (version NP_000894.1). For example, an altered level of a NQO1 polypeptide (or an mRNA encoding a NQO1 polypeptide) can be any level that is at least 1- fold different than a reference level of the NQO1 polypeptide (or a reference level of an mRNA encoding a NQO1 polypeptide). For example, an increased level of an mRNA encoding a NQO1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding a NQO1 polypeptide. For example, a decreased level of an mRNA encoding a NQO1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding a NQO1 polypeptide. In some cases, an altered level of a polypeptide (or mRNA) can be an altered level (e.g., an increased level increased level or a decreased level) of an ALDH1A1 polypeptide Attorney Docket No.07039-2153WO1 / 2022-168 (or an altered level of an mRNA encoding an ALDH1A1 polypeptide). An example of an ALDH1A1 polypeptide is, without limitation, the polypeptide set forth in the NCBI databases at, for example, NP_000680 (version NP_000680.2). For example, an altered level of an ALDH1A1 polypeptide (or an mRNA encoding an ALDH1A1 polypeptide) can be any level that is at least 1-fold different than a reference level of the ALDH1A1 polypeptide (or a reference level of an mRNA encoding an ALDH1A1 polypeptide). For example, an increased level of an mRNA encoding an ALDH1A1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of mRNA encoding an ALDH1A1 polypeptide. For example, a decreased level of an mRNA encoding an ALDH1A1 polypeptide can be a level that is at least 1 (e.g., at least 1.5, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold less than a reference level of mRNA encoding an ALDH1A1 polypeptide. Any appropriate method can be used to determine the presence, absence, or level of a polypeptide or mRNA encoding that polypeptide. In some cases, the presence, absence, or level of an mRNA encoding a polypeptide can be assessed by detecting and/or quantifying the mRNA encoding a polypeptide. Examples of methods that can be used to detect and/or quantify mRNA include, without limitation, RT-PCR techniques (e.g., quantitative RT-PCR techniques), bulk RNA-seq technology platforms, and NanoString platforms. In some cases, the presence, absence, or level of a polypeptide can be assessed by detecting and/or quantifying the polypeptide. Examples of methods that can be used to detect and/or quantify polypeptides include, without limitation, immunohistochemistry (IHC) techniques, mass spectrometry techniques (e.g., proteomics-based mass spectrometry assays or targeted quantification-based mass spectrometry assays), and western blotting techniques. In some cases, the presence, absence, or level of a polypeptide and/or mRNA encoding that polypeptide can be identified as described in Example 1, Example 2, Example 3, or Example 4. Any appropriate sample from a mammal (e.g., a human) having a cSCC can be assessed as described herein (e.g., for the molecular signature of the cSCC). In some cases, a sample can be a biological sample. In some cases, a sample can contain one or more cancer Attorney Docket No.07039-2153WO1 / 2022-168 cells (e.g., cSCC cells). In some cases, a sample can contain one or more biological molecules (e.g., nucleic acids such as DNA and RNA, polypeptides, carbohydrates, lipids, hormones, and/or metabolites). Examples of samples that can be assessed as described herein include, without limitation, tissue samples (e.g., skin samples). A sample can be a fresh sample or a fixed sample (e.g., a formaldehyde-fixed sample or a formalin-fixed sample). In some cases, one or more biological molecules can be isolated from a sample (e.g., from one or more cancer cells within the sample). For example, nucleic acid can be isolated from a sample and can be assessed as described herein. For example, polypeptides can be isolated from a sample and can be assessed as described herein. In some cases, the molecular signature of a cSCC can be used to identify a mammal (e.g., a human) having the cSCC as being likely to experience prolonged survival from cSCC (e.g., prolonged survival from the time of cSCC diagnosis). For example, the presence of one or more of an altered level of a BIRC5 polypeptide (or mRNA encoding a BIRC5 polypeptide), an altered level of a MELK polypeptide (or mRNA encoding a MELK polypeptide), an altered level of an IFNE polypeptide (or mRNA encoding an IFNE polypeptide), an altered level of a HMGCS1 polypeptide (or mRNA encoding a HMGCS1 polypeptide), an altered level of an ANK2 polypeptide (or mRNA encoding an ANK2 polypeptide), an altered level of a LAMA2 polypeptide (or mRNA encoding a LAMA2 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a FAM13C polypeptide (or mRNA encoding a FAM13C polypeptide), an altered level of a COL25A1 polypeptide (or mRNA encoding a COL25A1 polypeptide), an altered level of a TG polypeptide (or mRNA encoding a TG polypeptide), an altered level of a FAT4 polypeptide (or mRNA encoding a FAT4 polypeptide), an altered level of an ACSL1 polypeptide (or mRNA encoding an ACSL1 polypeptide), an altered level of an ALDH1A1 polypeptide (or mRNA encoding an ALDH1A1 polypeptide), an altered level of an ALDH3A2 polypeptide (or mRNA encoding an ALDH3A2 polypeptide), an altered level of an ALOX12 polypeptide (or mRNA encoding an ALOX12 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered Attorney Docket No.07039-2153WO1 / 2022-168 level of a CDCA5 polypeptide (or mRNA encoding a CDCA5 polypeptide), an altered level of a CEP55 polypeptide (or mRNA encoding a CEP55 polypeptide), an altered level of a CXCL8 polypeptide (or mRNA encoding a CXCL8 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a KRT2 polypeptide (or mRNA encoding a KRT2 polypeptide), an altered level of a NQO1 polypeptide (or mRNA encoding a NQO1 polypeptide), an altered level of a PRC1 polypeptide (or mRNA encoding a PRC1 polypeptide), an altered level of a TSGA10 polypeptide (or mRNA encoding a TSGA10 polypeptide), and an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide) in a sample (e.g., a tissue sample containing one or more cSCC cells) obtained from a mammal (e.g., a human) having a cSCC can be used to identify the mammal as being likely to experience prolonged survival from cSCC. In some cases, the presence of each of an altered level of a BIRC5 polypeptide (or mRNA encoding a BIRC5 polypeptide), an altered level of a MELK polypeptide (or mRNA encoding a MELK polypeptide), an altered level of an IFNE polypeptide (or mRNA encoding an IFNE polypeptide), an altered level of a HMGCS1 polypeptide (or mRNA encoding a HMGCS1 polypeptide), an altered level of an ANK2 polypeptide (or mRNA encoding an ANK2 polypeptide), an altered level of a LAMA2 polypeptide (or mRNA encoding a LAMA2 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a FAM13C polypeptide (or mRNA encoding a FAM13C polypeptide), an altered level of a COL25A1 polypeptide (or mRNA encoding a COL25A1 polypeptide), an altered level of a TG polypeptide (or mRNA encoding a TG polypeptide), and an altered level of a FAT4 polypeptide (or mRNA encoding a FAT4 polypeptide) in a sample (e.g., a tissue sample containing one or more cSCC cells) obtained from a mammal (e.g., a human) having a cSCC can be used to identify the mammal as being likely to experience prolonged survival from cSCC. In some cases, the presence of each of an altered level of an ACSL1 polypeptide (or mRNA encoding an ACSL1 polypeptide), an altered level of an ALDH1A1 polypeptide (or mRNA encoding an ALDH1A1 polypeptide), an altered level of an ALDH3A2 polypeptide (or mRNA encoding an ALDH3A2 polypeptide), an altered level of an ALOX12 polypeptide (or mRNA encoding an ALOX12 Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of a CDCA5 polypeptide (or mRNA encoding a CDCA5 polypeptide), an altered level of a CEP55 polypeptide (or mRNA encoding a CEP55 polypeptide), an altered level of a CXCL8 polypeptide (or mRNA encoding a CXCL8 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a KRT2 polypeptide (or mRNA encoding a KRT2 polypeptide), an altered level of a NQO1 polypeptide (or mRNA encoding a NQO1 polypeptide), an altered level of a PRC1 polypeptide (or mRNA encoding a PRC1 polypeptide), an altered level of a TSGA10 polypeptide (or mRNA encoding a TSGA10 polypeptide), and an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide) in a sample (e.g., a tissue sample containing one or more cSCC cells) obtained from a mammal (e.g., a human) having a cSCC can be used to identify the mammal as being likely to experience prolonged survival from cSCC. In some cases, the presence of each of an altered level of an ACSL1 polypeptide (or mRNA encoding an ACSL1 polypeptide), an altered level of an ALDH3A2 polypeptide (or mRNA encoding an ALDH3A2 polypeptide), an altered level of an ALOX12 polypeptide (or mRNA encoding an ALOX12 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a CDCA5 polypeptide (or mRNA encoding a CDCA5 polypeptide), an altered level of a CEP55 polypeptide (or mRNA encoding a CEP55 polypeptide), an altered level of a CXCL8 polypeptide (or mRNA encoding a CXCL8 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a KRT2 polypeptide (or mRNA encoding a KRT2 polypeptide), an altered level of a PRC1 polypeptide (or mRNA encoding a PRC1 polypeptide), and an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide) in a sample (e.g., a tissue sample containing one or more cSCC cells) obtained Attorney Docket No.07039-2153WO1 / 2022-168 from a mammal (e.g., a human) having a cSCC can be used to identify the mammal as being likely to experience prolonged survival from cSCC. In some cases, the presence of each of an altered level of an ALDH1A1 polypeptide (or mRNA encoding an ALDH1A1 polypeptide), an altered level of an ALDH3A2 polypeptide (or mRNA encoding an ALDH3A2 polypeptide), an altered level of an ALOX12 polypeptide (or mRNA encoding an ALOX12 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of a CDCA5 polypeptide (or mRNA encoding a CDCA5 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a NQO1 polypeptide (or mRNA encoding a NQO1 polypeptide), an altered level of a TSGA10 polypeptide (or mRNA encoding a TSGA10 polypeptide), and an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide) in a sample (e.g., a tissue sample containing one or more cSCC cells) obtained from a mammal (e.g., a human) having a cSCC can be used to identify the mammal as being likely to experience prolonged survival from cSCC. In some cases, the molecular signature of a cSCC can be used to identify a mammal (e.g., a human) having the cSCC as not being likely to experience prolonged survival from cSCC (e.g., prolonged survival from the time of cSCC diagnosis). For example, the absence of an altered level of a BIRC5 polypeptide (or mRNA encoding a BIRC5 polypeptide), an altered level of a MELK polypeptide (or mRNA encoding a MELK polypeptide), an altered level of an IFNE polypeptide (or mRNA encoding an IFNE polypeptide), an altered level of a HMGCS1 polypeptide (or mRNA encoding a HMGCS1 polypeptide), an altered level of an ANK2 polypeptide (or mRNA encoding an ANK2 polypeptide), an altered level of a LAMA2 polypeptide (or mRNA encoding a LAMA2 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a FAM13C polypeptide (or mRNA encoding a FAM13C polypeptide), an altered level of a COL25A1 polypeptide (or mRNA encoding a COL25A1 polypeptide), an altered level of a TG polypeptide (or mRNA encoding a TG polypeptide), an altered level of a FAT4 polypeptide (or mRNA encoding a FAT4 polypeptide), an altered level of an ACSL1 polypeptide (or mRNA encoding an ACSL1 polypeptide), an altered level of an ALDH1A1 polypeptide (or mRNA encoding an ALDH1A1 polypeptide), an altered level of an Attorney Docket No.07039-2153WO1 / 2022-168 ALDH3A2 polypeptide (or mRNA encoding an ALDH3A2 polypeptide), an altered level of an ALOX12 polypeptide (or mRNA encoding an ALOX12 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of a CDCA5 polypeptide (or mRNA encoding a CDCA5 polypeptide), an altered level of a CEP55 polypeptide (or mRNA encoding a CEP55 polypeptide), an altered level of a CXCL8 polypeptide (or mRNA encoding a CXCL8 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a KRT2 polypeptide (or mRNA encoding a KRT2 polypeptide), an altered level of a NQO1 polypeptide (or mRNA encoding a NQO1 polypeptide), an altered level of a PRC1 polypeptide (or mRNA encoding a PRC1 polypeptide), an altered level of a TSGA10 polypeptide (or mRNA encoding a TSGA10 polypeptide), and an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide) in a sample (e.g., a tissue sample containing one or more cSCC cells) obtained from a mammal (e.g., a human) having a cSCC can be used to identify the mammal as not being likely to experience prolonged survival from cSCC. In some cases, a mammal (e.g., a human) having a cSCC that is identified as being likely to experience prolonged survival from cSCC (e.g., prolonged survival from the time of cSCC diagnosis) as described herein (e.g., based, at least in part, on the molecular signature of the cSCC) can be selected to receive surgery to remove the cSCC. For example, a mammal having a cSCC that is identified as having a molecular signature that includes the presence of one or more of an altered level of a BIRC5 polypeptide (or mRNA encoding a BIRC5 polypeptide), an altered level of a MELK polypeptide (or mRNA encoding a MELK polypeptide), an altered level of an IFNE polypeptide (or mRNA encoding an IFNE polypeptide), an altered level of a HMGCS1 polypeptide (or mRNA encoding a HMGCS1 polypeptide), an altered level of an ANK2 polypeptide (or mRNA encoding an ANK2 polypeptide), an altered level of a LAMA2 polypeptide (or mRNA encoding a LAMA2 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide), an altered level of a FAM13C polypeptide (or mRNA encoding a FAM13C polypeptide), an altered level of a COL25A1 polypeptide (or mRNA encoding a COL25A1 polypeptide), an altered level of a TG polypeptide (or mRNA encoding a TG polypeptide), an altered level of a FAT4 polypeptide (or mRNA encoding a FAT4 polypeptide), an altered level of an ACSL1 polypeptide (or mRNA encoding an ACSL1 polypeptide), an altered level of an ALDH1A1 polypeptide (or mRNA encoding an ALDH1A1 polypeptide), an altered level of an ALDH3A2 polypeptide (or mRNA encoding an ALDH3A2 polypeptide), an altered level of an ALOX12 polypeptide (or mRNA encoding an ALOX12 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of a CDCA5 polypeptide (or mRNA encoding a CDCA5 polypeptide), an altered level of a CEP55 polypeptide (or mRNA encoding a CEP55 polypeptide), an altered level of a CXCL8 polypeptide (or mRNA encoding a CXCL8 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a KRT2 polypeptide (or mRNA encoding a KRT2 polypeptide), an altered level of a NQO1 polypeptide (or mRNA encoding a NQO1 polypeptide), an altered level of a PRC1 polypeptide (or mRNA encoding a PRC1 polypeptide), an altered level of a TSGA10 polypeptide (or mRNA encoding a TSGA10 polypeptide), and an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide) can be selected to undergo surgery to remove the cSCC (e.g., in the absence of any adjuvant therapies). In some cases, a mammal (e.g., a human) having a cSCC and identified as being unlikely to experience prolonged survival from cSCC (e.g., prolonged survival from the time of cSCC diagnosis) as described herein (e.g., based, at least in part, on the molecular signature of the cSCC) can be selected to receive surgery to remove the cSCC and can be selected for increased monitoring. For example a mammal having a cSCC that is identified as having a molecular signature that lacks the an altered level of a BIRC5 polypeptide (or mRNA encoding a BIRC5 polypeptide), an altered level of a MELK polypeptide (or mRNA encoding a MELK polypeptide), an altered level of an IFNE polypeptide (or mRNA encoding Attorney Docket No.07039-2153WO1 / 2022-168 an IFNE polypeptide), an altered level of a HMGCS1 polypeptide (or mRNA encoding a HMGCS1 polypeptide), an altered level of an ANK2 polypeptide (or mRNA encoding an ANK2 polypeptide), an altered level of a LAMA2 polypeptide (or mRNA encoding a LAMA2 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a FAM13C polypeptide (or mRNA encoding a FAM13C polypeptide), an altered level of a COL25A1 polypeptide (or mRNA encoding a COL25A1 polypeptide), an altered level of a TG polypeptide (or mRNA encoding a TG polypeptide), an altered level of a FAT4 polypeptide (or mRNA encoding a FAT4 polypeptide), an altered level of an ACSL1 polypeptide (or mRNA encoding an ACSL1 polypeptide), an altered level of an ALDH1A1 polypeptide (or mRNA encoding an ALDH1A1 polypeptide), an altered level of an ALDH3A2 polypeptide (or mRNA encoding an ALDH3A2 polypeptide), an altered level of an ALOX12 polypeptide (or mRNA encoding an ALOX12 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of a CDCA5 polypeptide (or mRNA encoding a CDCA5 polypeptide), an altered level of a CEP55 polypeptide (or mRNA encoding a CEP55 polypeptide), an altered level of a CXCL8 polypeptide (or mRNA encoding a CXCL8 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a KRT2 polypeptide (or mRNA encoding a KRT2 polypeptide), an altered level of a NQO1 polypeptide (or mRNA encoding a NQO1 polypeptide), an altered level of a PRC1 polypeptide (or mRNA encoding a PRC1 polypeptide), an altered level of a TSGA10 polypeptide (or mRNA encoding a TSGA10 polypeptide), and an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide) can be selected for increased monitoring such as receiving one or more (e.g., one, two, three, four, five, or more) tests that can be used to identify whether or not a cSCC is likely to metastasize. In some cases, a mammal (e.g., a human) having a cSCC and identified as being unlikely to experience prolonged survival from cSCC (e.g., prolonged survival from the time Attorney Docket No.07039-2153WO1 / 2022-168 of cSCC diagnosis) as described herein (e.g., based, at least in part, on the molecular signature of the cSCC) can be selected to receive surgery to remove the cSCC and can be selected for treatment with one or more adjuvant therapies. For example, a mammal having a cSCC that is identified as having a molecular signature that lacks the presence of one or more of an altered level of a BIRC5 polypeptide (or mRNA encoding a BIRC5 polypeptide), an altered level of a MELK polypeptide (or mRNA encoding a MELK polypeptide), an altered level of an IFNE polypeptide (or mRNA encoding an IFNE polypeptide), an altered level of a HMGCS1 polypeptide (or mRNA encoding a HMGCS1 polypeptide), an altered level of an ANK2 polypeptide (or mRNA encoding an ANK2 polypeptide), an altered level of a LAMA2 polypeptide (or mRNA encoding a LAMA2 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a FAM13C polypeptide (or mRNA encoding a FAM13C polypeptide), an altered level of a COL25A1 polypeptide (or mRNA encoding a COL25A1 polypeptide), an altered level of a TG polypeptide (or mRNA encoding a TG polypeptide), an altered level of a FAT4 polypeptide (or mRNA encoding a FAT4 polypeptide), an altered level of an ACSL1 polypeptide (or mRNA encoding an ACSL1 polypeptide), an altered level of an ALDH1A1 polypeptide (or mRNA encoding an ALDH1A1 polypeptide), an altered level of an ALDH3A2 polypeptide (or mRNA encoding an ALDH3A2 polypeptide), an altered level of an ALOX12 polypeptide (or mRNA encoding an ALOX12 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of a CDCA5 polypeptide (or mRNA encoding a CDCA5 polypeptide), an altered level of a CEP55 polypeptide (or mRNA encoding a CEP55 polypeptide), an altered level of a CXCL8 polypeptide (or mRNA encoding a CXCL8 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a KRT2 polypeptide (or mRNA encoding a KRT2 polypeptide), an altered level of a NQO1 polypeptide (or mRNA encoding a NQO1 polypeptide), an altered level of a PRC1 polypeptide (or mRNA encoding a PRC1 polypeptide), an altered level of a TSGA10 Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide (or mRNA encoding a TSGA10 polypeptide), and an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide) can be selected to undergo surgery to remove the cSCC and to receive one or more (e.g., one, two, three, four, five, or more) adjuvant therapies. In some cases, the molecular signature of a cSCC can be used to identify the cSCC as being likely to metastasize. For example, the presence of one or more of an altered level of a CSAG1 polypeptide (or mRNA encoding a CSAG1 polypeptide), an altered level of an UBE2C polypeptide (or mRNA encoding an UBE2C polypeptide), an altered level of an ANKRD1 polypeptide (or mRNA encoding an ANKRD1 polypeptide), an altered level of a CSMD3 polypeptide (or mRNA encoding a CSMD3 polypeptide), an altered level of a TOP2A polypeptide (or mRNA encoding a TOP2A polypeptide), an altered level of a TPX2 polypeptide (or mRNA encoding a TPX2 polypeptide), an altered level of a KSR2 polypeptide (or mRNA encoding a KSR2 polypeptide), an altered level of a CSMD2 polypeptide (or mRNA encoding a CSMD2 polypeptide), an altered level of a MMP20 polypeptide (or mRNA encoding a MMP20 polypeptide), an altered level of a PCSK1 polypeptide (or mRNA encoding a PCSK1 polypeptide), an altered level of a TMEM150B polypeptide (or mRNA encoding a TMEM150B polypeptide), an altered level of an ACSL1 polypeptide (or mRNA encoding an ACSL1 polypeptide), an altered level of a TSGA10 polypeptide (or mRNA encoding a TSGA10 polypeptide), an altered level of a KIT polypeptide (or mRNA encoding a KIT polypeptide), an altered level of a RGL3 polypeptide (or mRNA encoding a RGL3 polypeptide), an altered level of a PLA2G6 polypeptide (or mRNA encoding a PLA2G6 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of a FN1 polypeptide (or mRNA encoding a FN1 polypeptide), an altered level of a MGAM polypeptide (or mRNA encoding a MGAM polypeptide), an altered level of an EVPL polypeptide (or mRNA encoding an EVPL polypeptide), an altered level of an AOX1 polypeptide (or mRNA encoding an AOX1 polypeptide), an altered level of a PLA2R1 polypeptide (or mRNA encoding a PLA2R1 polypeptide), an altered level of a TRPM1 polypeptide (or mRNA encoding a TRPM1 Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a CYP4F22 polypeptide (or mRNA encoding a CYP4F22 polypeptide), an altered level of a CERS3 polypeptide (or mRNA encoding a CERS3 polypeptide), an altered level of a KIT polypeptide (or mRNA encoding a KIT polypeptide), an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a CYP2E1 polypeptide (or mRNA encoding a CYP2E1 polypeptide), and an altered level of a FASN polypeptide (or mRNA encoding a FASN polypeptide) in a sample (e.g., a tissue sample containing one or more cSCC cells) obtained from a mammal (e.g., a human) having a cSCC can be used to identify the cSCC as being likely to metastasize. In some cases, the presence of an altered level of a CSAG1 polypeptide (or mRNA encoding a CSAG1 polypeptide), an altered level of an UBE2C polypeptide (or mRNA encoding an UBE2C polypeptide), an altered level of an ANKRD1 polypeptide (or mRNA encoding an ANKRD1 polypeptide), an altered level of a CSMD3 polypeptide (or mRNA encoding a CSMD3 polypeptide), an altered level of a TOP2A polypeptide (or mRNA encoding a TOP2A polypeptide), an altered level of a TPX2 polypeptide (or mRNA encoding a TPX2 polypeptide), an altered level of a KSR2 polypeptide (or mRNA encoding a KSR2 polypeptide), an altered level of a CSMD2 polypeptide (or mRNA encoding a CSMD2 polypeptide), an altered level of a MMP20 polypeptide (or mRNA encoding a MMP20 polypeptide), an altered level of a PCSK1 polypeptide (or mRNA encoding a PCSK1 polypeptide), an altered level of a TMEM150B polypeptide (or mRNA encoding a TMEM150B polypeptide), an altered level of an ACSL1 polypeptide (or mRNA encoding an ACSL1 polypeptide), an altered level of a TSGA10 polypeptide (or mRNA encoding a TSGA10 polypeptide), an altered level of a KIT polypeptide (or mRNA encoding a KIT polypeptide), an altered level of a RGL3 polypeptide (or mRNA encoding a RGL3 polypeptide), and an altered level of a PLA2G6 polypeptide (or mRNA encoding a PLA2G6 polypeptide) in a sample (e.g., a tissue sample containing one or more cSCC cells) obtained from a mammal (e.g., a human) having a cSCC can be used to identify the cSCC as being likely to metastasize. In some cases, the presence of an altered level of an altered level of a Attorney Docket No.07039-2153WO1 / 2022-168 CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of a FN1 polypeptide (or mRNA encoding a FN1 polypeptide), an altered level of a MGAM polypeptide (or mRNA encoding a MGAM polypeptide), an altered level of an EVPL polypeptide (or mRNA encoding an EVPL polypeptide), an altered level of an AOX1 polypeptide (or mRNA encoding an AOX1 polypeptide), an altered level of a PLA2R1 polypeptide (or mRNA encoding a PLA2R1 polypeptide), an altered level of a TRPM1 polypeptide (or mRNA encoding a TRPM1 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a CYP4F22 polypeptide (or mRNA encoding a CYP4F22 polypeptide), an altered level of a CERS3 polypeptide (or mRNA encoding a CERS3 polypeptide), an altered level of a KIT polypeptide (or mRNA encoding a KIT polypeptide), an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a CYP2E1 polypeptide (or mRNA encoding a CYP2E1 polypeptide), and an altered level of a FASN polypeptide (or mRNA encoding a FASN polypeptide) in a sample (e.g., a tissue sample containing one or more cSCC cells) obtained from a mammal (e.g., a human) having a cSCC can be used to identify the cSCC as being likely to metastasize. In some cases, the molecular signature of a cSCC can be used to identify a cSCC as not being likely to metastasize. For example, the absence of an altered level of a CSAG1 polypeptide (or mRNA encoding a CSAG1 polypeptide), an altered level of an UBE2C polypeptide (or mRNA encoding an UBE2C polypeptide), an altered level of an ANKRD1 polypeptide (or mRNA encoding an ANKRD1 polypeptide), an altered level of a CSMD3 polypeptide (or mRNA encoding a CSMD3 polypeptide), an altered level of a TOP2A polypeptide (or mRNA encoding a TOP2A polypeptide), an altered level of a TPX2 polypeptide (or mRNA encoding a TPX2 polypeptide), an altered level of a KSR2 polypeptide (or mRNA encoding a KSR2 polypeptide), an altered level of a CSMD2 polypeptide (or mRNA encoding a CSMD2 polypeptide), an altered level of a MMP20 Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide (or mRNA encoding a MMP20 polypeptide), an altered level of a PCSK1 polypeptide (or mRNA encoding a PCSK1 polypeptide), an altered level of a TMEM150B polypeptide (or mRNA encoding a TMEM150B polypeptide), an altered level of an ACSL1 polypeptide (or mRNA encoding an ACSL1 polypeptide), an altered level of a TSGA10 polypeptide (or mRNA encoding a TSGA10 polypeptide), an altered level of a KIT polypeptide (or mRNA encoding a KIT polypeptide), an altered level of a RGL3 polypeptide (or mRNA encoding a RGL3 polypeptide), an altered level of a PLA2G6 polypeptide (or mRNA encoding a PLA2G6 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of a FN1 polypeptide (or mRNA encoding a FN1 polypeptide), an altered level of a MGAM polypeptide (or mRNA encoding a MGAM polypeptide), an altered level of an EVPL polypeptide (or mRNA encoding an EVPL polypeptide), an altered level of an AOX1 polypeptide (or mRNA encoding an AOX1 polypeptide), an altered level of a PLA2R1 polypeptide (or mRNA encoding a PLA2R1 polypeptide), an altered level of a TRPM1 polypeptide (or mRNA encoding a TRPM1 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a CYP4F22 polypeptide (or mRNA encoding a CYP4F22 polypeptide), an altered level of a CERS3 polypeptide (or mRNA encoding a CERS3 polypeptide), an altered level of a KIT polypeptide (or mRNA encoding a KIT polypeptide), an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a CYP2E1 polypeptide (or mRNA encoding a CYP2E1 polypeptide), and an altered level of a FASN polypeptide (or mRNA encoding a FASN polypeptide) in a sample (e.g., a tissue sample containing one or more cSCC cells) obtained from a mammal (e.g., a human) having a cSCC can be used to identify the cSCC as not being likely to metastasize. In some cases, a mammal (e.g., a human) having a cSCC that is identified as not being likely to metastasize (e.g., not likely to metastasize to one or more lymph nodes) as Attorney Docket No.07039-2153WO1 / 2022-168 described herein (e.g., based, at least in part, on the molecular signature of the cSCC) can be selected to receive surgery to remove the cSCC. For example, a mammal having a cSCC that is identified as having a molecular signature that lacks an altered level of a CSAG1 polypeptide (or mRNA encoding a CSAG1 polypeptide), an altered level of an UBE2C polypeptide (or mRNA encoding an UBE2C polypeptide), an altered level of an ANKRD1 polypeptide (or mRNA encoding an ANKRD1 polypeptide), an altered level of a CSMD3 polypeptide (or mRNA encoding a CSMD3 polypeptide), an altered level of a TOP2A polypeptide (or mRNA encoding a TOP2A polypeptide), an altered level of a TPX2 polypeptide (or mRNA encoding a TPX2 polypeptide), an altered level of a KSR2 polypeptide (or mRNA encoding a KSR2 polypeptide), an altered level of a CSMD2 polypeptide (or mRNA encoding a CSMD2 polypeptide), an altered level of a MMP20 polypeptide (or mRNA encoding a MMP20 polypeptide), an altered level of a PCSK1 polypeptide (or mRNA encoding a PCSK1 polypeptide), an altered level of a TMEM150B polypeptide (or mRNA encoding a TMEM150B polypeptide), an altered level of an ACSL1 polypeptide (or mRNA encoding an ACSL1 polypeptide), an altered level of a TSGA10 polypeptide (or mRNA encoding a TSGA10 polypeptide), an altered level of a KIT polypeptide (or mRNA encoding a KIT polypeptide), an altered level of a RGL3 polypeptide (or mRNA encoding a RGL3 polypeptide), an altered level of a PLA2G6 polypeptide (or mRNA encoding a PLA2G6 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of a FN1 polypeptide (or mRNA encoding a FN1 polypeptide), an altered level of a MGAM polypeptide (or mRNA encoding a MGAM polypeptide), an altered level of an EVPL polypeptide (or mRNA encoding an EVPL polypeptide), an altered level of an AOX1 polypeptide (or mRNA encoding an AOX1 polypeptide), an altered level of a PLA2R1 polypeptide (or mRNA encoding a PLA2R1 polypeptide), an altered level of a TRPM1 polypeptide (or mRNA encoding a TRPM1 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a CYP4F22 polypeptide (or mRNA encoding a CYP4F22 polypeptide), an altered level of a CERS3 polypeptide (or mRNA encoding a CERS3 Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide), an altered level of a KIT polypeptide (or mRNA encoding a KIT polypeptide), an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a CYP2E1 polypeptide (or mRNA encoding a CYP2E1 polypeptide), and an altered level of a FASN polypeptide (or mRNA encoding a FASN polypeptide) can be selected to undergo surgery to remove the cSCC (e.g., in the absence of any adjuvant therapies). In some cases, a mammal (e.g., a human) having a cSCC that is identified as being likely to metastasize (e.g., likely to metastasize to one or more lymph nodes) as described herein (e.g., based, at least in part, on the molecular signature of the cSCC) can be selected to receive surgery to remove the cSCC and can be selected for increased monitoring. For example, a mammal having a cSCC that is identified as having a molecular signature that includes one or more of an altered level of a CSAG1 polypeptide (or mRNA encoding a CSAG1 polypeptide), an altered level of an UBE2C polypeptide (or mRNA encoding an UBE2C polypeptide), an altered level of an ANKRD1 polypeptide (or mRNA encoding an ANKRD1 polypeptide), an altered level of a CSMD3 polypeptide (or mRNA encoding a CSMD3 polypeptide), an altered level of a TOP2A polypeptide (or mRNA encoding a TOP2A polypeptide), an altered level of a TPX2 polypeptide (or mRNA encoding a TPX2 polypeptide), an altered level of a KSR2 polypeptide (or mRNA encoding a KSR2 polypeptide), an altered level of a CSMD2 polypeptide (or mRNA encoding a CSMD2 polypeptide), an altered level of a MMP20 polypeptide (or mRNA encoding a MMP20 polypeptide), an altered level of a PCSK1 polypeptide (or mRNA encoding a PCSK1 polypeptide), an altered level of a TMEM150B polypeptide (or mRNA encoding a TMEM150B polypeptide), an altered level of an ACSL1 polypeptide (or mRNA encoding an ACSL1 polypeptide), an altered level of a TSGA10 polypeptide (or mRNA encoding a TSGA10 polypeptide), an altered level of a KIT polypeptide (or mRNA encoding a KIT polypeptide), an altered level of a RGL3 polypeptide (or mRNA encoding a RGL3 polypeptide), an altered level of a PLA2G6 polypeptide (or mRNA encoding a PLA2G6 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of a FN1 polypeptide (or mRNA encoding a FN1 polypeptide), an altered level of a MGAM polypeptide (or mRNA encoding a MGAM polypeptide), an altered level of an EVPL polypeptide (or mRNA encoding an EVPL polypeptide), an altered level of an AOX1 polypeptide (or mRNA encoding an AOX1 polypeptide), an altered level of a PLA2R1 polypeptide (or mRNA encoding a PLA2R1 polypeptide), an altered level of a TRPM1 polypeptide (or mRNA encoding a TRPM1 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a CYP4F22 polypeptide (or mRNA encoding a CYP4F22 polypeptide), an altered level of a CERS3 polypeptide (or mRNA encoding a CERS3 polypeptide), an altered level of a KIT polypeptide (or mRNA encoding a KIT polypeptide), an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a CYP2E1 polypeptide (or mRNA encoding a CYP2E1 polypeptide), and an altered level of a FASN polypeptide (or mRNA encoding a FASN polypeptide) can be selected to undergo surgery to remove the cSCC and to receive one or more (e.g., one, two, three, four, five, or more) tests that can be used to identify whether or not cSCC is likely to metastasize. In some cases, a mammal (e.g., a human) having a cSCC that is identified as being likely to metastasize (e.g., likely to metastasize to one or more lymph nodes) as described herein (e.g., based, at least in part, on the molecular signature of the cSCC) can be selected to receive surgery to remove the cSCC and can be selected for treatment with one or more adjuvant therapies. For example, a mammal having a cSCC that is identified as having a molecular signature that includes one or more of an altered level of a CSAG1 polypeptide (or mRNA encoding a CSAG1 polypeptide), an altered level of an UBE2C polypeptide (or mRNA encoding an UBE2C polypeptide), an altered level of an ANKRD1 polypeptide (or mRNA encoding an ANKRD1 polypeptide), an altered level of a CSMD3 polypeptide (or mRNA encoding a CSMD3 polypeptide), an altered level of a TOP2A polypeptide (or mRNA encoding a TOP2A polypeptide), an altered level of a TPX2 polypeptide (or mRNA Attorney Docket No.07039-2153WO1 / 2022-168 encoding a TPX2 polypeptide), an altered level of a KSR2 polypeptide (or mRNA encoding a KSR2 polypeptide), an altered level of a CSMD2 polypeptide (or mRNA encoding a CSMD2 polypeptide), an altered level of a MMP20 polypeptide (or mRNA encoding a MMP20 polypeptide), an altered level of a PCSK1 polypeptide (or mRNA encoding a PCSK1 polypeptide), an altered level of a TMEM150B polypeptide (or mRNA encoding a TMEM150B polypeptide), an altered level of an ACSL1 polypeptide (or mRNA encoding an ACSL1 polypeptide), an altered level of a TSGA10 polypeptide (or mRNA encoding a TSGA10 polypeptide), an altered level of a KIT polypeptide (or mRNA encoding a KIT polypeptide), an altered level of a RGL3 polypeptide (or mRNA encoding a RGL3 polypeptide), and an altered level of a PLA2G6 polypeptide (or mRNA encoding a PLA2G6 polypeptide) can be selected to undergo surgery to remove the cSCC and to receive one or more (e.g., one, two, three, four, five, or more) adjuvant therapies. For example, a mammal having a cSCC that is identified as having a molecular signature that includes one or more of an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of a FN1 polypeptide (or mRNA encoding a FN1 polypeptide), an altered level of a MGAM polypeptide (or mRNA encoding a MGAM polypeptide), an altered level of an EVPL polypeptide (or mRNA encoding an EVPL polypeptide), an altered level of an AOX1 polypeptide (or mRNA encoding an AOX1 polypeptide), an altered level of a PLA2R1 polypeptide (or mRNA encoding a PLA2R1 polypeptide), an altered level of a TRPM1 polypeptide (or mRNA encoding a TRPM1 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a CYP4F22 polypeptide (or mRNA encoding a CYP4F22 polypeptide), an altered level of a CERS3 polypeptide (or mRNA encoding a CERS3 polypeptide), an altered level of a KIT polypeptide (or mRNA encoding a KIT polypeptide), an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a CYP2E1 polypeptide (or mRNA encoding a CYP2E1 polypeptide), and an altered level of a FASN Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide (or mRNA encoding a FASN polypeptide) can be selected to undergo surgery to remove the cSCC and to receive one or more (e.g., one, two, three, four, five, or more) adjuvant therapies. This document also provides methods for treating a mammal (e.g., a human) having cSCC. In some cases, a mammal (e.g., a human) having a cSCC and assessed as described herein (e.g., to determine whether or not the mammal is likely to experience prolonged survival from cSCC (e.g., prolonged survival from the time of cSCC diagnosis) based, at least in part, on the molecular signature of the cSCC and/or to determine whether or not the cSCC is likely to metastasize based, at least in part, on the molecular signature of the cSCC) can be administered or instructed to self-administer one or more (e.g., one, two, three, four, five, or more) cancer treatments, where the one or more cancer treatments are effective to treat the cancer within the mammal. For example, a mammal having a cSCC can be administered or instructed to self-administer one or more cancer treatments selected based, at least in part, on whether or not the cSCC is likely to metastasize (e.g., based, at least in part, on the molecular signature of the cSCC). In general, a cancer treatment for cSCC can include any appropriate cSCC treatment. In some cases, a cancer treatment for cSCC can include surgery and other medical interventions. Examples of surgeries and other medical interventions that can be performed on a mammal having a cSCC to treat the mammal include, without limitation, surgery (e.g., to remove a cSCC, to remove the tissue around a cSCC, and to remove a cSCC and the surrounding tissue), and radiation therapy. In some cases, a cancer treatment can include administering one or more anti-cancer drugs (e.g., chemotherapeutic agents, targeted cancer drugs, and immunotherapy drugs) to a mammal in need thereof. In some cases, an anti-cancer drug can be an EGFR inhibitor. Examples of anti-cancer drugs that can be administered to a mammal having a cSCC can include, without limitation, cemiplimab-rwlc (e.g., LIBTAYO®), nivolumab (e.g., OPDIVO®), ipilimumab (e.g., YERVOY®), pembrolizumab (e.g., KEYTRUDA®), talimogene laherparepvec (T-VEC; e.g., IMLYGIC®), cetuximab (e.g., ERBITUX), capecitabine (e.g., XELODA®),
Figure imgf000086_0001
(5-FU), and combinations thereof. Attorney Docket No.07039-2153WO1 / 2022-168 When treating a mammal (e.g., a human) having a cSCC and identified as being likely to experience prolonged survival from cSCC (e.g., prolonged survival from the time of cSCC diagnosis) as described herein (e.g., based, at least in part, on the molecular signature of the cSCC), the mammal can undergo surgery to remove the cSCC. For example, a mammal having a cSCC that is identified as having a molecular signature that includes the presence of one or more an altered level of a BIRC5 polypeptide (or mRNA encoding a BIRC5 polypeptide), an altered level of a MELK polypeptide (or mRNA encoding a MELK polypeptide), an altered level of an IFNE polypeptide (or mRNA encoding an IFNE polypeptide), an altered level of a HMGCS1 polypeptide (or mRNA encoding a HMGCS1 polypeptide), an altered level of an ANK2 polypeptide (or mRNA encoding an ANK2 polypeptide), an altered level of a LAMA2 polypeptide (or mRNA encoding a LAMA2 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a FAM13C polypeptide (or mRNA encoding a FAM13C polypeptide), an altered level of a COL25A1 polypeptide (or mRNA encoding a COL25A1 polypeptide), an altered level of a TG polypeptide (or mRNA encoding a TG polypeptide), an altered level of a FAT4 polypeptide (or mRNA encoding a FAT4 polypeptide), an altered level of an ACSL1 polypeptide (or mRNA encoding an ACSL1 polypeptide), an altered level of an ALDH1A1 polypeptide (or mRNA encoding an ALDH1A1 polypeptide), an altered level of an ALDH3A2 polypeptide (or mRNA encoding an ALDH3A2 polypeptide), an altered level of an ALOX12 polypeptide (or mRNA encoding an ALOX12 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of a CDCA5 polypeptide (or mRNA encoding a CDCA5 polypeptide), an altered level of a CEP55 polypeptide (or mRNA encoding a CEP55 polypeptide), an altered level of a CXCL8 polypeptide (or mRNA encoding a CXCL8 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a KRT2 polypeptide (or mRNA encoding a KRT2 polypeptide), an altered level of a NQO1 polypeptide (or mRNA encoding a NQO1 polypeptide), an altered level of a PRC1 Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide (or mRNA encoding a PRC1 polypeptide), an altered level of a TSGA10 polypeptide (or mRNA encoding a TSGA10 polypeptide), and an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide) can undergo surgery to remove the cSCC (e.g., in the absence of any adjuvant therapies). When treating a mammal (e.g., a human) having a cSCC and identified as not being likely to experience prolonged survival from cSCC (e.g., prolonged survival from the time of cSCC diagnosis) as described herein (e.g., based, at least in part, on the molecular signature of the cSCC), the mammal can undergo surgery to remove the cSCC and can be administered or instructed to self-administer one or more adjuvant therapies. For example, a mammal having a cSCC that is identified as having a molecular signature that lacks the presence of an altered level of a BIRC5 polypeptide (or mRNA encoding a BIRC5 polypeptide), an altered level of a MELK polypeptide (or mRNA encoding a MELK polypeptide), an altered level of an IFNE polypeptide (or mRNA encoding an IFNE polypeptide), an altered level of a HMGCS1 polypeptide (or mRNA encoding a HMGCS1 polypeptide), an altered level of an ANK2 polypeptide (or mRNA encoding an ANK2 polypeptide), an altered level of a LAMA2 polypeptide (or mRNA encoding a LAMA2 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a FAM13C polypeptide (or mRNA encoding a FAM13C polypeptide), an altered level of a COL25A1 polypeptide (or mRNA encoding a COL25A1 polypeptide), an altered level of a TG polypeptide (or mRNA encoding a TG polypeptide), an altered level of a FAT4 polypeptide (or mRNA encoding a FAT4 polypeptide), an altered level of an ACSL1 polypeptide (or mRNA encoding an ACSL1 polypeptide), an altered level of an ALDH1A1 polypeptide (or mRNA encoding an ALDH1A1 polypeptide), an altered level of an ALDH3A2 polypeptide (or mRNA encoding an ALDH3A2 polypeptide), an altered level of an ALOX12 polypeptide (or mRNA encoding an ALOX12 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of a CDCA5 polypeptide (or mRNA encoding a CDCA5 polypeptide), an altered level of a CEP55 polypeptide (or mRNA encoding a CEP55 polypeptide), an altered level of a CXCL8 Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide (or mRNA encoding a CXCL8 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a KRT2 polypeptide (or mRNA encoding a KRT2 polypeptide), an altered level of a NQO1 polypeptide (or mRNA encoding a NQO1 polypeptide), an altered level of a PRC1 polypeptide (or mRNA encoding a PRC1 polypeptide), an altered level of a TSGA10 polypeptide (or mRNA encoding a TSGA10 polypeptide), and an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide) can be selected to undergo surgery to remove the cSCC and to receive one or more (e.g., one, two, three, four, five, or more) adjuvant therapies. When treating a mammal (e.g., a human) having a cSCC identified as not being likely to metastasize as described herein (e.g., based, at least in part, on the molecular signature of the cSCC), the mammal can undergo surgery to remove the cSCC. For example, a mammal having a cSCC that is identified as having a molecular signature that lacks an altered level of a CSAG1 polypeptide (or mRNA encoding a CSAG1 polypeptide), an altered level of an UBE2C polypeptide (or mRNA encoding an UBE2C polypeptide), an altered level of an ANKRD1 polypeptide (or mRNA encoding an ANKRD1 polypeptide), an altered level of a CSMD3 polypeptide (or mRNA encoding a CSMD3 polypeptide), an altered level of a TOP2A polypeptide (or mRNA encoding a TOP2A polypeptide), an altered level of a TPX2 polypeptide (or mRNA encoding a TPX2 polypeptide), an altered level of a KSR2 polypeptide (or mRNA encoding a KSR2 polypeptide), an altered level of a CSMD2 polypeptide (or mRNA encoding a CSMD2 polypeptide), an altered level of a MMP20 polypeptide (or mRNA encoding a MMP20 polypeptide), an altered level of a PCSK1 polypeptide (or mRNA encoding a PCSK1 polypeptide), an altered level of a TMEM150B polypeptide (or mRNA encoding a TMEM150B polypeptide), an altered level of an ACSL1 polypeptide (or mRNA encoding an ACSL1 polypeptide), an altered level of a TSGA10 polypeptide (or mRNA encoding a TSGA10 polypeptide), an altered level of a KIT polypeptide (or mRNA encoding a KIT polypeptide), an altered level of a RGL3 polypeptide (or mRNA encoding a RGL3 polypeptide), an altered level of a PLA2G6 polypeptide (or mRNA encoding a PLA2G6 polypeptide), an altered level of a CYP2U1 polypeptide (or Attorney Docket No.07039-2153WO1 / 2022-168 mRNA encoding a CYP2U1 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of a FN1 polypeptide (or mRNA encoding a FN1 polypeptide), an altered level of a MGAM polypeptide (or mRNA encoding a MGAM polypeptide), an altered level of an EVPL polypeptide (or mRNA encoding an EVPL polypeptide), an altered level of an AOX1 polypeptide (or mRNA encoding an AOX1 polypeptide), an altered level of a PLA2R1 polypeptide (or mRNA encoding a PLA2R1 polypeptide), an altered level of a TRPM1 polypeptide (or mRNA encoding a TRPM1 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a CYP4F22 polypeptide (or mRNA encoding a CYP4F22 polypeptide), an altered level of a CERS3 polypeptide (or mRNA encoding a CERS3 polypeptide), an altered level of a KIT polypeptide (or mRNA encoding a KIT polypeptide), an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a CYP2E1 polypeptide (or mRNA encoding a CYP2E1 polypeptide), and an altered level of a FASN polypeptide (or mRNA encoding a FASN polypeptide) can undergo surgery to remove the cSCC (e.g., in the absence of any adjuvant therapies). When treating a mammal (e.g., a human) having a cSCC identified as being likely to metastasize as described herein (e.g., based, at least in part, on the molecular signature of the cSCC), the mammal can undergo surgery to remove the cSCC and can be administered or instructed to self-administer one or more adjuvant therapies. For example, a mammal having a cSCC that is identified as having a molecular signature that includes one or more of an altered level of a CSAG1 polypeptide (or mRNA encoding a CSAG1 polypeptide), an altered level of an UBE2C polypeptide (or mRNA encoding an UBE2C polypeptide), an altered level of an ANKRD1 polypeptide (or mRNA encoding an ANKRD1 polypeptide), an altered level of a CSMD3 polypeptide (or mRNA encoding a CSMD3 polypeptide), an altered level of a TOP2A polypeptide (or mRNA encoding a TOP2A polypeptide), an altered level of a TPX2 polypeptide (or mRNA encoding a TPX2 polypeptide), an altered level of a KSR2 polypeptide (or mRNA encoding a KSR2 polypeptide), an altered level of a CSMD2 Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide (or mRNA encoding a CSMD2 polypeptide), an altered level of a MMP20 polypeptide (or mRNA encoding a MMP20 polypeptide), an altered level of a PCSK1 polypeptide (or mRNA encoding a PCSK1 polypeptide), an altered level of a TMEM150B polypeptide (or mRNA encoding a TMEM150B polypeptide), an altered level of an ACSL1 polypeptide (or mRNA encoding an ACSL1 polypeptide), an altered level of a TSGA10 polypeptide (or mRNA encoding a TSGA10 polypeptide), an altered level of a KIT polypeptide (or mRNA encoding a KIT polypeptide), an altered level of a RGL3 polypeptide (or mRNA encoding a RGL3 polypeptide), an altered level of a PLA2G6 polypeptide (or mRNA encoding a PLA2G6 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of a FN1 polypeptide (or mRNA encoding a FN1 polypeptide), an altered level of a MGAM polypeptide (or mRNA encoding a MGAM polypeptide), an altered level of an EVPL polypeptide (or mRNA encoding an EVPL polypeptide), an altered level of an AOX1 polypeptide (or mRNA encoding an AOX1 polypeptide), an altered level of a PLA2R1 polypeptide (or mRNA encoding a PLA2R1 polypeptide), an altered level of a TRPM1 polypeptide (or mRNA encoding a TRPM1 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a CYP4F22 polypeptide (or mRNA encoding a CYP4F22 polypeptide), an altered level of a CERS3 polypeptide (or mRNA encoding a CERS3 polypeptide), an altered level of a KIT polypeptide (or mRNA encoding a KIT polypeptide), an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a CYP2E1 polypeptide (or mRNA encoding a CYP2E1 polypeptide), and an altered level of a FASN polypeptide (or mRNA encoding a FASN polypeptide) can be selected to undergo surgery to remove the cSCC and to receive one or more (e.g., one, two, three, four, five, or more) adjuvant therapies. An adjuvant therapy can be any appropriate cancer treatment. In some cases, a cancer treatment that can be used as an adjuvant therapy with surgery to treat a mammal (e.g., a Attorney Docket No.07039-2153WO1 / 2022-168 human) having a cSCC and identified as not being likely to experience prolonged survival from cSCC (e.g., prolonged survival from the time of cSCC diagnosis) and/or identified as having a cSCC that is likely to metastasize as described herein (e.g., based, at least in part, on the molecular signature of the cSCC) can include, without limitation, radiation therapy. In some cases, a cancer treatment that can be used as an adjuvant therapy with surgery to treat a mammal having a cSCC and identified as not being likely to experience prolonged survival from cSCC as described herein and/or identified as having a cSCC that is likely to metastasize as described herein can include administering one or more anti-cancer drugs (e.g., chemotherapeutic agents, targeted cancer drugs, and immunotherapy drugs) to the mammal. Examples of anti-cancer drugs that can be administered to a mammal having a cSCC can include, without limitation, cemiplimab-rwlc (e.g., LIBTAYO®), nivolumab (e.g., OPDIVO®), ipilimumab (e.g., YERVOY®), pembrolizumab (e.g., KEYTRUDA®), talimogene laherparepvec (T-VEC; e.g., IMLYGIC®), cetuximab (e.g., ERBITUX), capecitabine (e.g., XELODA®), carboplatin, 5-FU, and combinations thereof. In some cases, when treating a mammal (e.g., a human) having a cSCC as described herein, the treatment can be effective to treat the cSCC. For example, the number of cancer cells present within a mammal can be reduced using the methods and materials described herein. In some cases, the methods and materials described herein can be used to reduce the number of cancer cells present within a mammal having a cSCC by, for example, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, or more percent. In some cases, the number of cancer cells present within a mammal does not increase. For example, the size (e.g., volume) of one or more tumors present within a mammal can be reduced using the methods and materials described herein. In some cases, the methods and materials described herein can be used to reduce the size of one or more tumors present within a mammal having a cSCC by, for example, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, or more percent. In some cases, the size (e.g., volume) of one or more tumors present within a mammal does not increase. In some cases, when treating a mammal (e.g., a human) having a cSCC as described herein, the treatment can be effective to treat the cSCC while minimizing the risk of metastasis. In some cases, when treating a mammal (e.g., a human) having a cSCC as described herein, the treatment can be effective to improve survival of the mammal. For example, a Attorney Docket No.07039-2153WO1 / 2022-168 mammal (e.g., a human) having a cSCC and identified as being likely to experience prolonged survival from cSCC (e.g., prolonged survival from the time of cSCC diagnosis) as described herein (e.g., based, at least in part, on the molecular signature of the cSCC) can experience a higher survival rate. For example, a mammal having a cSCC that is identified as having a molecular signature that includes the presence of one or more of an altered level of a BIRC5 polypeptide (or mRNA encoding a BIRC5 polypeptide), an altered level of a MELK polypeptide (or mRNA encoding a MELK polypeptide), an altered level of an IFNE polypeptide (or mRNA encoding an IFNE polypeptide), an altered level of a HMGCS1 polypeptide (or mRNA encoding a HMGCS1 polypeptide), an altered level of an ANK2 polypeptide (or mRNA encoding an ANK2 polypeptide), an altered level of a LAMA2 polypeptide (or mRNA encoding a LAMA2 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a FAM13C polypeptide (or mRNA encoding a FAM13C polypeptide), an altered level of a COL25A1 polypeptide (or mRNA encoding a COL25A1 polypeptide), an altered level of a TG polypeptide (or mRNA encoding a TG polypeptide), an altered level of a FAT4 polypeptide (or mRNA encoding a FAT4 polypeptide), an altered level of an ACSL1 polypeptide (or mRNA encoding an ACSL1 polypeptide), an altered level of an ALDH1A1 polypeptide (or mRNA encoding an ALDH1A1 polypeptide), an altered level of an ALDH3A2 polypeptide (or mRNA encoding an ALDH3A2 polypeptide), an altered level of an ALOX12 polypeptide (or mRNA encoding an ALOX12 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of a CDCA5 polypeptide (or mRNA encoding a CDCA5 polypeptide), an altered level of a CEP55 polypeptide (or mRNA encoding a CEP55 polypeptide), an altered level of a CXCL8 polypeptide (or mRNA encoding a CXCL8 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a KRT2 polypeptide (or mRNA encoding a KRT2 polypeptide), an altered level of a NQO1 polypeptide (or mRNA encoding a NQO1 polypeptide), an altered level of a PRC1 Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide (or mRNA encoding a PRC1 polypeptide), an altered level of a TSGA10 polypeptide (or mRNA encoding a TSGA10 polypeptide), and an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide) can experience a higher survival rate (e.g., as compared to a mammal such as a human having cSCC and identified as having a molecular signature that lacks and increased level of each of these polypeptides (or mRNA encoding each polypeptide). In some cases, a prolonged survival from cSCC can be survival (e.g., overall survival or disease-free survival) that is longer than 2 years (e.g., from the diagnosis of the cSCC). For example, the methods and materials described herein can be used to improve survival (e.g., overall survival or disease-free survival). For example, the methods and materials described herein can be used to improve overall survival. For example, the methods and materials described herein can be used to improve the survival of a mammal having a cSCC by, for example, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, or more percent. For example, the methods and materials described herein can be used to improve the survival of a mammal having a cSCC by, for example, at least 6 months (e.g., about 6 months, about 8 months, about 10 months, about 1 year, about 1.5 years, about 2 years, about 2.5 years, or about 3 years). In some cases, when treating a mammal (e.g., a human) having a cSCC as described herein, the treatment can be effective to improve survival of the mammal while minimizing the risk of metastasis. In some cases, when treating a mammal (e.g., a human) having a cSCC as described herein, the treatment can be effective to reduce or eliminate one or more symptoms of the cSCC. Examples of symptoms of cSCC that can be reduced or eliminated using the methods and materials described herein can include, without limitation, firm and red nodules, flat sores (e.g., with a scaly crust), raised areas on old scars, ulcers, rough patches on the lip and/or inside the mouth, scaly patches on the lip, open sores on the lip and/or inside the mouth, pain, and swelling (e.g., lymphedema). For example, the methods and materials described herein can be used to reduce one or more symptoms of cSCC within a mammal having a cSCC by, for example, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, or more percent. In some cases, when treating a mammal (e.g., a human) having a cSCC as described herein, the treatment can be effective to reduce or eliminate one or more symptoms of the cSCC while minimizing the risk of metastasis. Attorney Docket No.07039-2153WO1 / 2022-168 In some cases, a course of treatment, the number of cancer cells present within a mammal and/or the severity of one or more symptoms related to the cSCC can be monitored. Any appropriate method can be used to determine whether or not the number of cancer cells present within a mammal is reduced. For example, imaging techniques can be used to assess the number of cancer cells present within a mammal. The invention will be further described in the following examples, which do not limit the scope of the invention described in the claims. EXAMPLES Example 1: Metastatic Potential of cSCC This example describes the identification of a gene expression signature for cSCC that can be used to predict whether or not a cSCC patient is at a higher risk of metastasis (e.g., nodal metastasis). Integrated genomics and transcriptomics of matched samples of intermediate and high-risk (T2a & T2b, as classified by Brigham Women’s Hospital Staging) cSCC were performed. Briefly, DNA sequencing of 61 samples (32 primary tumors that did not metastasize and 29 that did metastasize) and RNA sequencing of 52 samples (30 primary tumors that did not metastasize and 22 that did metastasize) was performed. These samples included both synchronous and asynchronous metastatic disease. Whole exome sequencing (WES) was used to characterize the genomic landscape of intermediate to high risk cSCC that did metastasize and the genomic landscape of intermediate to high risk cSCC that did not metastasize. Whole transcriptome sequencing using DESeq2 was also performed, and 24 differentially expressed genes were identified (CDKN2A, LAMA2, RGL3, COL22A1, VEGFC, KLF17, NXF1, MIIP, CYP3A5, CSMD3, CLK4, AOX1, CXCL9, ANO4, CENPO, EMCN, GPR111, INMT, LHFPL3, GPLD1, LRP1B, SCN8A, SPP1, and MYRIP). Functional enrichment analysis using Gene Ontology (GO) was performed, which identified 23 upregulated pathways and 11 downregulated pathways with p<0.05 after adjusting for false discovery rate. StringDB was used to identify regulatory hub genes (those with the highest number of known gene interactions) within these pathways. Attorney Docket No.07039-2153WO1 / 2022-168 The top regulatory hub genes, 25 from upregulated pathways and 25 from downregulated pathways, were also added to the gene expression profile panel. Two genes overlapped between the whole exome/transcriptome and regulatory hub gene sets, leaving a total of 72 genes for version 1 of the cSCC risk stratification gene expression profile panel. The 72 genes were analyzed using a Partitioning Around Medoids (PAM) method for gene clustering. All 72 genes were found to cluster in 6 distinct groups, which allowed for a smaller predictive gene panel. Univariate Cox regression was used to select the genes that are potentially associated with overall survival and metastasis. Each marker was identified based on having at least 1-fold change on the Log 2 normalized data (log2 fold change), which means 1-fold change in the normalized data was twofold change in the gene expression raw count data in RNA-seq. The significance of changes in genes was assessed using DEseq2 R software package using a negative binomial GLM to test each gene. The markers were selected based on two criteria: (1) log2 fold change > 1 (upregulated) or < -1 (downregulated), and (2) p values from the negative binomial GLM model < 0.05 which was adjusted for multiple testing for correcting false positive rate (adjusted p values < 0.05). The housekeeping genes used to identify markers are shown in Table 1 and were selected based on the following characteristics: 1) gene expression level was no different between the cancer and control groups (e.g., based on FDR-adjusted p values), 2) variation in the genes was relatively small (e.g., less than 1 in the log2 normalized expression data), 3) gene expression was at a detectable level (e.g., higher than 85% of all genes in the RNA-seq cohort (>10)), and 4) protein-coding genes. Table 1. House-keeping genes used to determine differential expression. Housekeeping Genes Log2 Median Expression Level
Figure imgf000096_0001
Attorney Docket No.07039-2153WO1 / 2022-168 SH3BP1 10.53 NUP133 10.75
Figure imgf000097_0002
There were 8 genes that were significantly altered in expression relative to normal skin at 0.10 level with overall survival – NXF1, CENPO, CXCL10, CXCL11, CXCL9, OAS2, LAMA2, and MYRIP. Based upon correlation and clustering, CXCL10, LAMA2, and MYRIP can be used to predict overall survival. On multivariable analysis, high risk gene score (2 or 3) was found to be an independent predictor of lower survival with a relative risk (RR) of 20.2 (Table 1).
Figure imgf000097_0001
There were seven genes that were altered in expression relative to normal skin and associated with metastasis at 0.10 level – ABCA12, FLG2, LCE2D, LOR, RGL3, OASL, and Attorney Docket No.07039-2153WO1 / 2022-168 INMT. Based upon correlation and clustering, FLG2, RGL3, OASL, and INMT can be used to predict metastasis. All metastatic patients had a metastatic genetic risk score of ≥2 for metastasis, while most non-metastatic patients a score of ≤2 (55% ^1 and 40%=2) (Table 2).
Figure imgf000098_0001
Using a threshold score of 2 to delineate high and low risk of metastasis, the assay properly stratifies 95% of non-metastatic intermediate to high risk tumors and 70% of metastatic intermediate to high risk tumors. Together these results demonstrate that the molecular signature of a cSCC can be used to predict the patient outcome, and can be used to select a treatment based on the predicted outcome(s). For example, an increased level of a NXF1 polypeptide (or mRNA encoding a NXF1 polypeptide), an increased level of a CENPO polypeptide (or mRNA encoding a CENPO polypeptide), an increased level of a CXCL10 polypeptide (or mRNA encoding a CXCL10 polypeptide), an increased level of a CXCL11 polypeptide (or mRNA encoding a CXCL11 polypeptide), an increased level of a CXCL9 polypeptide (or mRNA encoding a CXCL9 polypeptide), an increased level of an OAS2 polypeptide (or mRNA encoding an OAS2 polypeptide), an increased level of a LAMA2 polypeptide (or mRNA Attorney Docket No.07039-2153WO1 / 2022-168 encoding a LAMA2 polypeptide), and/or an increased level of a MYRIP polypeptide (or mRNA encoding a MYRIP polypeptide), in a cancer cells of a mammal (e.g., a human) having a cSCC can be used to identify that mammal as being likely to experience improved survival (e.g., overall survival). In another example, an increased level of an ABCA12 polypeptide (or mRNA encoding an ABCA12 polypeptide), an increased level of a FLG2 polypeptide (or mRNA encoding a FLG2 polypeptide), an increased level of a LCE2D polypeptide (or mRNA encoding a LCE2D polypeptide), an increased level of a LOR polypeptide (or mRNA encoding a LOR polypeptide), an increased level of a RGL3 polypeptide (or mRNA encoding a RGL3 polypeptide), an increased level of an OASL polypeptide (or mRNA encoding an OASL polypeptide), and/or an increased level of an INMT polypeptide (or mRNA encoding an INMT polypeptide), in a cancer cells of a mammal (e.g., a human) having a cSCC can be used to identify that cSCC as being likely to metastasize (e.g., likely to metastasize to one or more lymph nodes). Example 2: cSCC RNA analysis This analysis looked at the differential expression levels of 183 genes – 50 were up- regulated, 50 were down-regulated, and 14 differed between metastatic and non-metastatic samples. Additional genes were differentially expressed from MutSig and OncoDrive analyses. For all the RNA sample data, the primary control sample data were removed. For patients with multiple primary tumor data, the 1st primary tumor sample data was used and subsequent sample data were excluded. Therefore, this analysis used a total of 50 patients (22 metastatic patients and 28 non-metastatic patients). Clustering analysis A partitioning around medoids (PAM) method was used to cluster the 183 genes into 9 clusters: 26 genes in cluster 1, 12 genes in cluster 2, 9 genes in cluster 3, 50 genes in cluster 4, 18 genes in cluster 5, 22 genes in cluster 6, 20 genes in cluster 7, 15 genes in cluster 8, and 11 genes in cluster 9. The genes were ordered based on their cluster order, and a heatmap was generated based on the Pearson correlation coefficients using their raw expression data. Genes within Attorney Docket No.07039-2153WO1 / 2022-168 cluster 1, 4, 5 and 6 were highly correlated with each other, genes within cluster 2 and 3 were moderately correlated with each other, and genes in clusters 7, 8, 9 were weakly correlated with each other (Figure 1). Patient Population Table 2 shows the patient demographics and clinical characteristics of metastatic patients (PMet) and non-metastatic patients (PNoMet). There was no significant difference in age at CSCC onset, sex, race, immunosuppressant use, or disease stage between the two groups. Table 2. Patient demographics and clinical characteristics.
Figure imgf000100_0001
Attorney Docket No.07039-2153WO1 / 2022-168 Gene summary statistics Table 3 shows the categorical data for each gene including demographics, clinical characteristics, and gene mutations by metastasic status. Table 3. Demographics, Clinical Characteristics, and Gene Mutations Comparison. PMet (N=22) PNoMet (N=28) Total (N=50) p value ABCA12 Mutation Categories 0.0701 Down regulated 18 (81.8%) 15 (53.6%) 33 (66.0%) No change 4 (18.2%) 13 (46.4%) 17 (34.0%) ALOX12 Mutation Categories No change 22 (100.0%) 28 (100.0%) 50 (100.0%) ALOX12B Mutation Categories 0.3941 Down regulated 14 (63.6%) 15 (53.6%) 29 (58.0%) No change 7 (31.8%) 8 (28.6%) 15 (30.0%) Up regulated 1 (4.5%) 5 (17.9%) 6 (12.0%) ALOX15 Mutation Categories No change 22 (100.0%) 28 (100.0%) 50 (100.0%) CASP14 Mutation Categories 0.1711 Down regulated 9 (40.9%) 7 (25.0%) 16 (32.0%) No change 12 (54.5%) 21 (75.0%) 33 (66.0%) Up regulated 1 (4.5%) 0 (0.0%) 1 (2.0%) CERS3 Mutation Categories 0.0211 Down regulated 19 (86.4%) 15 (53.6%) 34 (68.0%) No change 3 (13.6%) 12 (42.9%) 15 (30.0%) Up regulated 0 (0.0%) 1 (3.6%) 1 (2.0%) CYP2E1 Mutation Categories 0.6581 Down regulated 13 (59.1%) 13 (46.4%) 26 (52.0%) Attorney Docket No.07039-2153WO1 / 2022-168 No change 9 (40.9%) 14 (50.0%) 23 (46.0%) Up regulated 0 (0.0%) 1 (3.6%) 1 (2.0%) CYP4F2 Mutation Categories No change 22 (100.0%) 28 (100.0%) 50 (100.0%) CYP4F22 Mutation Categories 0.0601 Down regulated 20 (90.9%) 19 (67.9%) 39 (78.0%) No change 1 (4.5%) 8 (28.6%) 9 (18.0%) Up regulated 1 (4.5%) 1 (3.6%) 2 (4.0%) DNAH3 Mutation Categories 1.0001 Down regulated 9 (40.9%) 10 (35.7%) 19 (38.0%) No change 13 (59.1%) 17 (60.7%) 30 (60.0%) Up regulated 0 (0.0%) 1 (3.6%) 1 (2.0%) EPHX2 Mutation Categories 1.0001 Down regulated 20 (90.9%) 26 (92.9%) 46 (92.0%) No change 2 (9.1%) 2 (7.1%) 4 (8.0%) EVPL Mutation Categories 0.0361 Down regulated 18 (81.8%) 14 (50.0%) 32 (64.0%) No change 4 (18.2%) 14 (50.0%) 18 (36.0%) EXPH5 Mutation Categories 0.4441 Down regulated 20 (90.9%) 23 (82.1%) 43 (86.0%) No change 2 (9.1%) 5 (17.9%) 7 (14.0%) FAM81B Mutation Categories 0.1311 No change 18 (81.8%) 17 (60.7%) 35 (70.0%) Up regulated 4 (18.2%) 11 (39.3%) 15 (30.0%) FCGBP Mutation Categories 0.9111 Down regulated 9 (40.9%) 10 (35.7%) 19 (38.0%) No change 11 (50.0%) 16 (57.1%) 27 (54.0%) Attorney Docket No.07039-2153WO1 / 2022-168 Up regulated 2 (9.1%) 2 (7.1%) 4 (8.0%) HMGCR Mutation Categories 0.2151 Down regulated 18 (81.8%) 18 (64.3%) 36 (72.0%) No change 4 (18.2%) 10 (35.7%) 14 (28.0%) HMGCS1 Mutation Categories 1.0001 Down regulated 5 (22.7%) 6 (21.4%) 11 (22.0%) No change 17 (77.3%) 22 (78.6%) 39 (78.0%) LCE6A Mutation Categories 0.0181 Down regulated 18 (81.8%) 13 (46.4%) 31 (62.0%) No change 3 (13.6%) 14 (50.0%) 17 (34.0%) Up regulated 1 (4.5%) 1 (3.6%) 2 (4.0%) NDRG4 Mutation Categories 0.9041 Down regulated 9 (40.9%) 10 (35.7%) 19 (38.0%) No change 12 (54.5%) 16 (57.1%) 28 (56.0%) Up regulated 1 (4.5%) 2 (7.1%) 3 (6.0%) PLA2G2F Mutation Categories 0.3151 Down regulated 4 (18.2%) 6 (21.4%) 10 (20.0%) No change 18 (81.8%) 19 (67.9%) 37 (74.0%) Up regulated 0 (0.0%) 3 (10.7%) 3 (6.0%) PLA2G4B Mutation Categories 0.1611 Down regulated 17 (77.3%) 17 (60.7%) 34 (68.0%) No change 4 (18.2%) 11 (39.3%) 15 (30.0%) Up regulated 1 (4.5%) 0 (0.0%) 1 (2.0%) PLA2G4D Mutation Categories 0.8381 Down regulated 1 (4.5%) 3 (10.7%) 4 (8.0%) No change 20 (90.9%) 23 (82.1%) 43 (86.0%) Up regulated 1 (4.5%) 2 (7.1%) 3 (6.0%) Attorney Docket No.07039-2153WO1 / 2022-168 PLA2G4E Mutation Categories 0.4301 Down regulated 12 (54.5%) 10 (35.7%) 22 (44.0%) No change 9 (40.9%) 17 (60.7%) 26 (52.0%) Up regulated 1 (4.5%) 1 (3.6%) 2 (4.0%) PLB1 Mutation Categories 0.2651 Down regulated 17 (77.3%) 18 (64.3%) 35 (70.0%) No change 4 (18.2%) 10 (35.7%) 14 (28.0%) Up regulated 1 (4.5%) 0 (0.0%) 1 (2.0%) PPL Mutation Categories 0.3051 Down regulated 16 (72.7%) 15 (53.6%) 31 (62.0%) No change 6 (27.3%) 12 (42.9%) 18 (36.0%) Up regulated 0 (0.0%) 1 (3.6%) 1 (2.0%) ZNF750 Mutation Categories 0.0781 Down regulated 17 (77.3%) 14 (50.0%) 31 (62.0%) No change 5 (22.7%) 13 (46.4%) 18 (36.0%) Up regulated 0 (0.0%) 1 (3.6%) 1 (2.0%) ABCB11 Mutation Categories 0.1691 Down regulated 10 (45.5%) 7 (25.0%) 17 (34.0%) No change 12 (54.5%) 18 (64.3%) 30 (60.0%) Up regulated 0 (0.0%) 3 (10.7%) 3 (6.0%) COL22A1 Mutation Categories 1.0001 No change 5 (22.7%) 7 (25.0%) 12 (24.0%) Up regulated 17 (77.3%) 21 (75.0%) 38 (76.0%) CSAG1 Mutation Categories 0.0831 No change 11 (50.0%) 21 (75.0%) 32 (64.0%) Up regulated 11 (50.0%) 7 (25.0%) 18 (36.0%) CSMD3 Mutation Categories 0.0861 Attorney Docket No.07039-2153WO1 / 2022-168 No change 6 (27.3%) 15 (53.6%) 21 (42.0%) Up regulated 16 (72.7%) 13 (46.4%) 29 (58.0%) DLGAP3 Mutation Categories 0.5591 No change 15 (68.2%) 16 (57.1%) 31 (62.0%) Up regulated 7 (31.8%) 12 (42.9%) 19 (38.0%) DMD Mutation Categories No change 22 (100.0%) 28 (100.0%) 50 (100.0%) MUC16 Mutation Categories 0.7531 No change 15 (68.2%) 21 (75.0%) 36 (72.0%) Up regulated 7 (31.8%) 7 (25.0%) 14 (28.0%) ORM1 Mutation Categories 0.0031 No change 21 (95.5%) 16 (57.1%) 37 (74.0%) Up regulated 1 (4.5%) 12 (42.9%) 13 (26.0%) ORM2 Mutation Categories 0.0141 No change 21 (95.5%) 18 (64.3%) 39 (78.0%) Up regulated 1 (4.5%) 10 (35.7%) 11 (22.0%) PKHD1L1 Mutation Categories No change 22 (100.0%) 28 (100.0%) 50 (100.0%) RGL3 Mutation Categories 0.0261 Down regulated 2 (9.1%) 11 (39.3%) 13 (26.0%) No change 19 (86.4%) 16 (57.1%) 35 (70.0%) Up regulated 1 (4.5%) 1 (3.6%) 2 (4.0%) SOAT2 Mutation Categories 0.2531 No change 10 (45.5%) 18 (64.3%) 28 (56.0%) Up regulated 12 (54.5%) 10 (35.7%) 22 (44.0%) ABHD5 Mutation Categories No change 22 (100.0%) 28 (100.0%) 50 (100.0%) Attorney Docket No.07039-2153WO1 / 2022-168 APOB Mutation Categories No change 22 (100.0%) 28 (100.0%) 50 (100.0%) CYP2C9 Mutation Categories 0.5591 Down regulated 15 (68.2%) 16 (57.1%) 31 (62.0%) No change 7 (31.8%) 12 (42.9%) 19 (38.0%) CYP3A5 Mutation Categories 0.5761 Down regulated 20 (90.9%) 27 (96.4%) 47 (94.0%) No change 2 (9.1%) 1 (3.6%) 3 (6.0%) DHCR7 Mutation Categories 1.0001 Down regulated 2 (9.1%) 2 (7.1%) 4 (8.0%) No change 20 (90.9%) 26 (92.9%) 46 (92.0%) KRT1 Mutation Categories 0.8411 Down regulated 19 (86.4%) 22 (78.6%) 41 (82.0%) No change 3 (13.6%) 5 (17.9%) 8 (16.0%) Up regulated 0 (0.0%) 1 (3.6%) 1 (2.0%) KRT10 Mutation Categories 1.0001 Down regulated 19 (86.4%) 25 (89.3%) 44 (88.0%) No change 3 (13.6%) 3 (10.7%) 6 (12.0%) KRT2 Mutation Categories No change 22 (100.0%) 28 (100.0%) 50 (100.0%) MSMO1 Mutation Categories No change 22 (100.0%) 28 (100.0%) 50 (100.0%) ACAT2 Mutation Categories 0.4971 Down regulated 0 (0.0%) 2 (7.1%) 2 (4.0%) No change 22 (100.0%) 26 (92.9%) 48 (96.0%) ASPM Mutation Categories 0.8521 Down regulated 0 (0.0%) 1 (3.6%) 1 (2.0%) Attorney Docket No.07039-2153WO1 / 2022-168 No change 5 (22.7%) 5 (17.9%) 10 (20.0%) Up regulated 17 (77.3%) 22 (78.6%) 39 (78.0%) AURKA Mutation Categories 0.5451 Down regulated 0 (0.0%) 1 (3.6%) 1 (2.0%) No change 2 (9.1%) 5 (17.9%) 7 (14.0%) Up regulated 20 (90.9%) 22 (78.6%) 42 (84.0%) AURKB Mutation Categories 0.5691 No change 8 (36.4%) 13 (46.4%) 21 (42.0%) Up regulated 14 (63.6%) 15 (53.6%) 29 (58.0%) BIRC5 Mutation Categories 0.2151 No change 4 (18.2%) 10 (35.7%) 14 (28.0%) Up regulated 18 (81.8%) 18 (64.3%) 36 (72.0%) BUB1 Mutation Categories 0.2111 No change 1 (4.5%) 5 (17.9%) 6 (12.0%) Up regulated 21 (95.5%) 23 (82.1%) 44 (88.0%) BUB1B Mutation Categories 0.3431 Down regulated 0 (0.0%) 1 (3.6%) 1 (2.0%) No change 2 (9.1%) 6 (21.4%) 8 (16.0%) Up regulated 20 (90.9%) 21 (75.0%) 41 (82.0%) CCNA2 Mutation Categories 1.0001 No change 7 (31.8%) 9 (32.1%) 16 (32.0%) Up regulated 15 (68.2%) 19 (67.9%) 34 (68.0%) CCNB1 Mutation Categories 0.5121 No change 4 (18.2%) 8 (28.6%) 12 (24.0%) Up regulated 18 (81.8%) 20 (71.4%) 38 (76.0%) CCNB2 Mutation Categories 1.0001 No change 5 (22.7%) 7 (25.0%) 12 (24.0%) Attorney Docket No.07039-2153WO1 / 2022-168 Up regulated 17 (77.3%) 21 (75.0%) 38 (76.0%) CDC20 Mutation Categories 0.4441 No change 2 (9.1%) 5 (17.9%) 7 (14.0%) Up regulated 20 (90.9%) 23 (82.1%) 43 (86.0%) CDC25C Mutation Categories 0.5001 Down regulated 0 (0.0%) 2 (7.1%) 2 (4.0%) No change 4 (18.2%) 7 (25.0%) 11 (22.0%) Up regulated 18 (81.8%) 19 (67.9%) 37 (74.0%) CDC6 Mutation Categories 0.1861 Down regulated 0 (0.0%) 1 (3.6%) 1 (2.0%) No change 3 (13.6%) 9 (32.1%) 12 (24.0%) Up regulated 19 (86.4%) 18 (64.3%) 37 (74.0%) CDCA5 Mutation Categories 1.0001 Down regulated 0 (0.0%) 1 (3.6%) 1 (2.0%) No change 2 (9.1%) 3 (10.7%) 5 (10.0%) Up regulated 20 (90.9%) 24 (85.7%) 44 (88.0%) CDCA8 Mutation Categories 0.1541 No change 2 (9.1%) 8 (28.6%) 10 (20.0%) Up regulated 20 (90.9%) 20 (71.4%) 40 (80.0%) CDK1 Mutation Categories 0.8411 Down regulated 0 (0.0%) 1 (3.6%) 1 (2.0%) No change 3 (13.6%) 5 (17.9%) 8 (16.0%) Up regulated 19 (86.4%) 22 (78.6%) 41 (82.0%) CENPE Mutation Categories 1.0001 Down regulated 1 (4.5%) 1 (3.6%) 2 (4.0%) No change 5 (22.7%) 7 (25.0%) 12 (24.0%) Up regulated 16 (72.7%) 20 (71.4%) 36 (72.0%) Attorney Docket No.07039-2153WO1 / 2022-168 CENPF Mutation Categories 0.4351 Down regulated 0 (0.0%) 1 (3.6%) 1 (2.0%) No change 5 (22.7%) 10 (35.7%) 15 (30.0%) Up regulated 17 (77.3%) 17 (60.7%) 34 (68.0%) CEP55 Mutation Categories 0.2661 No change 2 (9.1%) 7 (25.0%) 9 (18.0%) Up regulated 20 (90.9%) 21 (75.0%) 41 (82.0%) CHEK1 Mutation Categories 0.4801 No change 3 (13.6%) 7 (25.0%) 10 (20.0%) Up regulated 19 (86.4%) 21 (75.0%) 40 (80.0%) DLGAP5 Mutation Categories 0.2661 No change 2 (9.1%) 7 (25.0%) 9 (18.0%) Up regulated 20 (90.9%) 21 (75.0%) 41 (82.0%) DNAH5 Mutation Categories 0.7781 No change 9 (40.9%) 13 (46.4%) 22 (44.0%) Up regulated 13 (59.1%) 15 (53.6%) 28 (56.0%) FOXM1 Mutation Categories 0.2461 Down regulated 0 (0.0%) 1 (3.6%) 1 (2.0%) No change 0 (0.0%) 3 (10.7%) 3 (6.0%) Up regulated 22 (100.0%) 24 (85.7%) 46 (92.0%) HJURP Mutation Categories 0.4391 No change 2 (9.1%) 6 (21.4%) 8 (16.0%) Up regulated 20 (90.9%) 22 (78.6%) 42 (84.0%) ITGA5 Mutation Categories 1.0001 No change 3 (13.6%) 5 (17.9%) 8 (16.0%) Up regulated 19 (86.4%) 23 (82.1%) 42 (84.0%) KIF11 Mutation Categories 0.7511 Attorney Docket No.07039-2153WO1 / 2022-168 No change 5 (22.7%) 8 (28.6%) 13 (26.0%) Up regulated 17 (77.3%) 20 (71.4%) 37 (74.0%) KIF20A Mutation Categories 0.3061 No change 3 (13.6%) 8 (28.6%) 11 (22.0%) Up regulated 19 (86.4%) 20 (71.4%) 39 (78.0%) KIF23 Mutation Categories 0.2461 No change 0 (0.0%) 3 (10.7%) 3 (6.0%) Up regulated 22 (100.0%) 25 (89.3%) 47 (94.0%) KIF2C Mutation Categories 0.8411 Down regulated 0 (0.0%) 1 (3.6%) 1 (2.0%) No change 3 (13.6%) 5 (17.9%) 8 (16.0%) Up regulated 19 (86.4%) 22 (78.6%) 41 (82.0%) KIF4A Mutation Categories 0.3681 No change 1 (4.5%) 4 (14.3%) 5 (10.0%) Up regulated 21 (95.5%) 24 (85.7%) 45 (90.0%) MAD2L1 Mutation Categories 0.7731 No change 8 (36.4%) 9 (32.1%) 17 (34.0%) Up regulated 14 (63.6%) 19 (67.9%) 33 (66.0%) MELK Mutation Categories 0.4391 No change 2 (9.1%) 6 (21.4%) 8 (16.0%) Up regulated 20 (90.9%) 22 (78.6%) 42 (84.0%) MKI67 Mutation Categories 0.3531 Down regulated 1 (4.5%) 2 (7.1%) 3 (6.0%) No change 2 (9.1%) 7 (25.0%) 9 (18.0%) Up regulated 19 (86.4%) 19 (67.9%) 38 (76.0%) NCAPG Mutation Categories 0.7341 No change 4 (18.2%) 7 (25.0%) 11 (22.0%) Attorney Docket No.07039-2153WO1 / 2022-168 Up regulated 18 (81.8%) 21 (75.0%) 39 (78.0%) NCAPH Mutation Categories 0.3681 No change 1 (4.5%) 4 (14.3%) 5 (10.0%) Up regulated 21 (95.5%) 24 (85.7%) 45 (90.0%) NDC80 Mutation Categories 0.7131 No change 3 (13.6%) 6 (21.4%) 9 (18.0%) Up regulated 19 (86.4%) 22 (78.6%) 41 (82.0%) NQO1 Mutation Categories 0.0991 No change 14 (63.6%) 24 (85.7%) 38 (76.0%) Up regulated 8 (36.4%) 4 (14.3%) 12 (24.0%) NUF2 Mutation Categories 0.6501 Down regulated 0 (0.0%) 2 (7.1%) 2 (4.0%) No change 5 (22.7%) 6 (21.4%) 11 (22.0%) Up regulated 17 (77.3%) 20 (71.4%) 37 (74.0%) NUSAP1 Mutation Categories 0.3051 Down regulated 0 (0.0%) 3 (10.7%) 3 (6.0%) No change 9 (40.9%) 8 (28.6%) 17 (34.0%) Up regulated 13 (59.1%) 17 (60.7%) 30 (60.0%) PBK Mutation Categories 1.0001 Down regulated 1 (4.5%) 1 (3.6%) 2 (4.0%) No change 6 (27.3%) 8 (28.6%) 14 (28.0%) Up regulated 15 (68.2%) 19 (67.9%) 34 (68.0%) PLK1 Mutation Categories 1.0001 No change 3 (13.6%) 4 (14.3%) 7 (14.0%) Up regulated 19 (86.4%) 24 (85.7%) 43 (86.0%) PRC1 Mutation Categories 1.0001 Down regulated 0 (0.0%) 1 (3.6%) 1 (2.0%) Attorney Docket No.07039-2153WO1 / 2022-168 No change 5 (22.7%) 6 (21.4%) 11 (22.0%) Up regulated 17 (77.3%) 21 (75.0%) 38 (76.0%) PTTG1 Mutation Categories 1.0001 No change 4 (18.2%) 5 (17.9%) 9 (18.0%) Up regulated 18 (81.8%) 23 (82.1%) 41 (82.0%) RRM2 Mutation Categories 1.0001 No change 3 (13.6%) 4 (14.3%) 7 (14.0%) Up regulated 19 (86.4%) 24 (85.7%) 43 (86.0%) SAGE1 Mutation Categories 1.0001 No change 12 (54.5%) 16 (57.1%) 28 (56.0%) Up regulated 10 (45.5%) 12 (42.9%) 22 (44.0%) SMC4 Mutation Categories 0.0591 Down regulated 0 (0.0%) 5 (17.9%) 5 (10.0%) No change 10 (45.5%) 7 (25.0%) 17 (34.0%) Up regulated 12 (54.5%) 16 (57.1%) 28 (56.0%) TOP2A Mutation Categories 0.3431 Down regulated 0 (0.0%) 1 (3.6%) 1 (2.0%) No change 2 (9.1%) 6 (21.4%) 8 (16.0%) Up regulated 20 (90.9%) 21 (75.0%) 41 (82.0%) TPX2 Mutation Categories 0.0601 No change 1 (4.5%) 8 (28.6%) 9 (18.0%) Up regulated 21 (95.5%) 20 (71.4%) 41 (82.0%) TTK Mutation Categories 1.0001 Down regulated 0 (0.0%) 1 (3.6%) 1 (2.0%) No change 4 (18.2%) 5 (17.9%) 9 (18.0%) Up regulated 18 (81.8%) 22 (78.6%) 40 (80.0%) UBE2C Mutation Categories 0.1171 Attorney Docket No.07039-2153WO1 / 2022-168 No change 1 (4.5%) 6 (21.4%) 7 (14.0%) Up regulated 21 (95.5%) 22 (78.6%) 43 (86.0%) ACSL1 Mutation Categories 0.3431 Down regulated 8 (36.4%) 6 (21.4%) 14 (28.0%) No change 14 (63.6%) 22 (78.6%) 36 (72.0%) ALOX15B Mutation Categories No change 22 (100.0%) 28 (100.0%) 50 (100.0%) CALCOCO1 Mutation Categories 1.0001 Down regulated 18 (81.8%) 23 (82.1%) 41 (82.0%) No change 4 (18.2%) 5 (17.9%) 9 (18.0%) CYP4A22 Mutation Categories No change 22 (100.0%) 28 (100.0%) 50 (100.0%) CYP4F3 Mutation Categories No change 22 (100.0%) 28 (100.0%) 50 (100.0%) DGAT2 Mutation Categories 0.4071 Down regulated 13 (59.1%) 13 (46.4%) 26 (52.0%) No change 9 (40.9%) 15 (53.6%) 24 (48.0%) FA2H Mutation Categories No change 22 (100.0%) 28 (100.0%) 50 (100.0%) FADS1 Mutation Categories No change 22 (100.0%) 28 (100.0%) 50 (100.0%) FADS2 Mutation Categories No change 22 (100.0%) 28 (100.0%) 50 (100.0%) FASN Mutation Categories No change 22 (100.0%) 28 (100.0%) 50 (100.0%) HMGCS2 Mutation Categories No change 22 (100.0%) 28 (100.0%) 50 (100.0%) Attorney Docket No.07039-2153WO1 / 2022-168 KRT28 Mutation Categories No change 22 (100.0%) 28 (100.0%) 50 (100.0%) LIPE Mutation Categories No change 22 (100.0%) 28 (100.0%) 50 (100.0%) PPARG Mutation Categories 0.7511 Down regulated 5 (22.7%) 8 (28.6%) 13 (26.0%) No change 17 (77.3%) 20 (71.4%) 37 (74.0%) TCHH Mutation Categories No change 22 (100.0%) 28 (100.0%) 50 (100.0%) THRSP Mutation Categories No change 22 (100.0%) 28 (100.0%) 50 (100.0%) TRPM1 Mutation Categories 0.0841 Down regulated 21 (95.5%) 20 (71.4%) 41 (82.0%) No change 1 (4.5%) 7 (25.0%) 8 (16.0%) Up regulated 0 (0.0%) 1 (3.6%) 1 (2.0%) TSGA10 Mutation Categories 0.0451 Down regulated 20 (90.9%) 18 (64.3%) 38 (76.0%) No change 2 (9.1%) 10 (35.7%) 12 (24.0%) ACTA1 Mutation Categories 0.2171 No change 17 (77.3%) 26 (92.9%) 43 (86.0%) Up regulated 5 (22.7%) 2 (7.1%) 7 (14.0%) ACTN2 Mutation Categories 0.1621 Down regulated 1 (4.5%) 4 (14.3%) 5 (10.0%) No change 11 (50.0%) 18 (64.3%) 29 (58.0%) Up regulated 10 (45.5%) 6 (21.4%) 16 (32.0%) ALDH1A1 Mutation Categories 1.0001 Down regulated 13 (59.1%) 17 (60.7%) 30 (60.0%) Attorney Docket No.07039-2153WO1 / 2022-168 No change 9 (40.9%) 11 (39.3%) 20 (40.0%) ANK2 Mutation Categories 0.0341 Down regulated 16 (72.7%) 27 (96.4%) 43 (86.0%) No change 6 (27.3%) 1 (3.6%) 7 (14.0%) CKM Mutation Categories 0.4811 No change 17 (77.3%) 24 (85.7%) 41 (82.0%) Up regulated 5 (22.7%) 4 (14.3%) 9 (18.0%) CMYA5 Mutation Categories 0.2571 Down regulated 18 (81.8%) 23 (82.1%) 41 (82.0%) No change 2 (9.1%) 5 (17.9%) 7 (14.0%) Up regulated 2 (9.1%) 0 (0.0%) 2 (4.0%) CYP2C19 Mutation Categories 1.0001 Down regulated 14 (63.6%) 18 (64.3%) 32 (64.0%) No change 8 (36.4%) 10 (35.7%) 18 (36.0%) CYP3A4 Mutation Categories 0.5591 Down regulated 17 (77.3%) 24 (85.7%) 41 (82.0%) No change 4 (18.2%) 4 (14.3%) 8 (16.0%) Up regulated 1 (4.5%) 0 (0.0%) 1 (2.0%) FCRL5 Mutation Categories 0.3601 No change 13 (59.1%) 21 (75.0%) 34 (68.0%) Up regulated 9 (40.9%) 7 (25.0%) 16 (32.0%) HSPB7 Mutation Categories No change 22 (100.0%) 28 (100.0%) 50 (100.0%) KRTAP5 Mutation Categories No change 22 (100.0%) 28 (100.0%) 50 (100.0%) KSR2 Mutation Categories 0.0061 No change 13 (59.1%) 26 (92.9%) 39 (78.0%) Attorney Docket No.07039-2153WO1 / 2022-168 Up regulated 9 (40.9%) 2 (7.1%) 11 (22.0%) LAMA2 Mutation Categories 0.7831 Down regulated 10 (45.5%) 14 (50.0%) 24 (48.0%) No change 12 (54.5%) 14 (50.0%) 26 (52.0%) MUC5B Mutation Categories 0.6431 No change 19 (86.4%) 26 (92.9%) 45 (90.0%) Up regulated 3 (13.6%) 2 (7.1%) 5 (10.0%) SCARA5 Mutation Categories 0.3681 Down regulated 1 (4.5%) 4 (14.3%) 5 (10.0%) No change 21 (95.5%) 24 (85.7%) 45 (90.0%) SLITRK3 Mutation Categories No change 22 (100.0%) 28 (100.0%) 50 (100.0%) SMPX Mutation Categories 0.0321 No change 15 (68.2%) 26 (92.9%) 41 (82.0%) Up regulated 7 (31.8%) 2 (7.1%) 9 (18.0%) SYNPO2L Mutation Categories 0.7611 No change 14 (63.6%) 20 (71.4%) 34 (68.0%) Up regulated 8 (36.4%) 8 (28.6%) 16 (32.0%) TNFRSF21 Mutation Categories 0.0841 No change 7 (31.8%) 3 (10.7%) 10 (20.0%) Up regulated 15 (68.2%) 25 (89.3%) 40 (80.0%) TNNI1 Mutation Categories 0.0841 No change 15 (68.2%) 25 (89.3%) 40 (80.0%) Up regulated 7 (31.8%) 3 (10.7%) 10 (20.0%) TTN Mutation Categories 0.3331 Down regulated 2 (9.1%) 4 (14.3%) 6 (12.0%) No change 13 (59.1%) 20 (71.4%) 33 (66.0%) Attorney Docket No.07039-2153WO1 / 2022-168 Up regulated 7 (31.8%) 4 (14.3%) 11 (22.0%) XIRP2 Mutation Categories 0.2771 No change 17 (77.3%) 25 (89.3%) 42 (84.0%) Up regulated 5 (22.7%) 3 (10.7%) 8 (16.0%) ALDH3A2 Mutation Categories 0.2661 Down regulated 20 (90.9%) 21 (75.0%) 41 (82.0%) No change 2 (9.1%) 7 (25.0%) 9 (18.0%) ARID3C Mutation Categories No change 22 (100.0%) 28 (100.0%) 50 (100.0%) COL11A1 Mutation Categories 0.5771 No change 9 (40.9%) 14 (50.0%) 23 (46.0%) Up regulated 13 (59.1%) 14 (50.0%) 27 (54.0%) CSMD1 Mutation Categories 0.1211 No change 22 (100.0%) 24 (85.7%) 46 (92.0%) Up regulated 0 (0.0%) 4 (14.3%) 4 (8.0%) CSMD2 Mutation Categories 0.2541 Down regulated 0 (0.0%) 1 (3.6%) 1 (2.0%) No change 8 (36.4%) 15 (53.6%) 23 (46.0%) Up regulated 14 (63.6%) 12 (42.9%) 26 (52.0%) CYP1A1 Mutation Categories No change 22 (100.0%) 28 (100.0%) 50 (100.0%) DGKI Mutation Categories 0.1541 Down regulated 0 (0.0%) 1 (3.6%) 1 (2.0%) No change 8 (36.4%) 16 (57.1%) 24 (48.0%) Up regulated 14 (63.6%) 11 (39.3%) 25 (50.0%) DNAJC5B Mutation Categories 1.0001 No change 13 (59.1%) 16 (57.1%) 29 (58.0%) Attorney Docket No.07039-2153WO1 / 2022-168 Up regulated 9 (40.9%) 12 (42.9%) 21 (42.0%) FAM178B Mutation Categories 1.0001 No change 11 (50.0%) 15 (53.6%) 26 (52.0%) Up regulated 11 (50.0%) 13 (46.4%) 24 (48.0%) FN1 Mutation Categories 0.7731 No change 8 (36.4%) 12 (42.9%) 20 (40.0%) Up regulated 14 (63.6%) 16 (57.1%) 30 (60.0%) KLF17 Mutation Categories 0.0611 No change 12 (54.5%) 23 (82.1%) 35 (70.0%) Up regulated 10 (45.5%) 5 (17.9%) 15 (30.0%) LRP1B Mutation Categories 0.7081 Down regulated 17 (77.3%) 22 (78.6%) 39 (78.0%) No change 4 (18.2%) 6 (21.4%) 10 (20.0%) Up regulated 1 (4.5%) 0 (0.0%) 1 (2.0%) MMP20 Mutation Categories 0.0421 No change 11 (50.0%) 22 (78.6%) 33 (66.0%) Up regulated 11 (50.0%) 6 (21.4%) 17 (34.0%) NKAIN3 Mutation Categories 1.0001 No change 22 (100.0%) 27 (96.4%) 49 (98.0%) Up regulated 0 (0.0%) 1 (3.6%) 1 (2.0%) PLA2G6 Mutation Categories 0.3201 Down regulated 10 (45.5%) 17 (60.7%) 27 (54.0%) No change 11 (50.0%) 11 (39.3%) 22 (44.0%) Up regulated 1 (4.5%) 0 (0.0%) 1 (2.0%) PLA2R1 Mutation Categories 1.0001 Down regulated 1 (4.5%) 2 (7.1%) 3 (6.0%) No change 21 (95.5%) 26 (92.9%) 47 (94.0%) Attorney Docket No.07039-2153WO1 / 2022-168 POTEM Mutation Categories 0.3021 No change 16 (72.7%) 24 (85.7%) 40 (80.0%) Up regulated 6 (27.3%) 4 (14.3%) 10 (20.0%) TG Mutation Categories 0.6911 Down regulated 0 (0.0%) 1 (3.6%) 1 (2.0%) No change 21 (95.5%) 27 (96.4%) 48 (96.0%) Up regulated 1 (4.5%) 0 (0.0%) 1 (2.0%) USH2A Mutation Categories 0.5451 Down regulated 2 (9.1%) 5 (17.9%) 7 (14.0%) No change 20 (90.9%) 22 (78.6%) 42 (84.0%) Up regulated 0 (0.0%) 1 (3.6%) 1 (2.0%) ZNF469 Mutation Categories 0.5691 No change 10 (45.5%) 16 (57.1%) 26 (52.0%) Up regulated 12 (54.5%) 12 (42.9%) 24 (48.0%) ANKRD1 Mutation Categories 0.0091 No change 12 (54.5%) 25 (89.3%) 37 (74.0%) Up regulated 10 (45.5%) 3 (10.7%) 13 (26.0%) AOX1 Mutation Categories 0.5691 Down regulated 14 (63.6%) 15 (53.6%) 29 (58.0%) No change 8 (36.4%) 13 (46.4%) 21 (42.0%) CXCL8 Mutation Categories 1.0001 No change 3 (13.6%) 4 (14.3%) 7 (14.0%) Up regulated 19 (86.4%) 24 (85.7%) 43 (86.0%) CYP2U1 Mutation Categories 0.5591 Down regulated 7 (31.8%) 12 (42.9%) 19 (38.0%) No change 15 (68.2%) 16 (57.1%) 31 (62.0%) CYP4A11 Mutation Categories Attorney Docket No.07039-2153WO1 / 2022-168 No change 22 (100.0%) 28 (100.0%) 50 (100.0%) FAM13C Mutation Categories 0.2461 Down regulated 22 (100.0%) 25 (89.3%) 47 (94.0%) No change 0 (0.0%) 3 (10.7%) 3 (6.0%) FAT4 Mutation Categories 1.0001 Down regulated 12 (54.5%) 15 (53.6%) 27 (54.0%) No change 9 (40.9%) 11 (39.3%) 20 (40.0%) Up regulated 1 (4.5%) 2 (7.1%) 3 (6.0%) FGF10 Mutation Categories No change 22 (100.0%) 28 (100.0%) 50 (100.0%) IL1B Mutation Categories 0.7651 No change 6 (27.3%) 9 (32.1%) 15 (30.0%) Up regulated 16 (72.7%) 19 (67.9%) 35 (70.0%) KIT Mutation Categories 0.0431 Down regulated 12 (54.5%) 7 (25.0%) 19 (38.0%) No change 10 (45.5%) 21 (75.0%) 31 (62.0%) MGAM Mutation Categories 0.5671 No change 12 (54.5%) 18 (64.3%) 30 (60.0%) Up regulated 10 (45.5%) 10 (35.7%) 20 (40.0%) RELN Mutation Categories 0.3431 Down regulated 2 (9.1%) 6 (21.4%) 8 (16.0%) No change 20 (90.9%) 21 (75.0%) 41 (82.0%) Up regulated 0 (0.0%) 1 (3.6%) 1 (2.0%) SVEP1 Mutation Categories 1.0001 Down regulated 12 (54.5%) 15 (53.6%) 27 (54.0%) No change 10 (45.5%) 13 (46.4%) 23 (46.0%) SYNE1 Mutation Categories 0.7761 Attorney Docket No.07039-2153WO1 / 2022-168 Down regulated 11 (50.0%) 16 (57.1%) 27 (54.0%) No change 11 (50.0%) 12 (42.9%) 23 (46.0%) UNC13C Mutation Categories 0.2461 Down regulated 22 (100.0%) 25 (89.3%) 47 (94.0%) No change 0 (0.0%) 3 (10.7%) 3 (6.0%) CDKN2A Mutation Categories 0.2111 No change 1 (4.5%) 5 (17.9%) 6 (12.0%) Up regulated 21 (95.5%) 23 (82.1%) 44 (88.0%) COL25A1 Mutation Categories 1.0001 Down regulated 3 (13.6%) 3 (10.7%) 6 (12.0%) No change 19 (86.4%) 25 (89.3%) 44 (88.0%) CXCL10 Mutation Categories 0.5121 No change 4 (18.2%) 8 (28.6%) 12 (24.0%) Up regulated 18 (81.8%) 20 (71.4%) 38 (76.0%) GRM8 Mutation Categories 0.0081 Down regulated 0 (0.0%) 1 (3.6%) 1 (2.0%) No change 4 (18.2%) 15 (53.6%) 19 (38.0%) Up regulated 18 (81.8%) 12 (42.9%) 30 (60.0%) IFNE Mutation Categories 0.2641 No change 8 (36.4%) 15 (53.6%) 23 (46.0%) Up regulated 14 (63.6%) 13 (46.4%) 27 (54.0%) PCSK1 Mutation Categories 0.0431 No change 10 (45.5%) 21 (75.0%) 31 (62.0%) Up regulated 12 (54.5%) 7 (25.0%) 19 (38.0%) RHAG Mutation Categories No change 22 (100.0%) 28 (100.0%) 50 (100.0%) RYR2 Mutation Categories 0.7271 Attorney Docket No.07039-2153WO1 / 2022-168 Down regulated 8 (36.4%) 9 (32.1%) 17 (34.0%) No change 12 (54.5%) 18 (64.3%) 30 (60.0%) Up regulated 2 (9.1%) 1 (3.6%) 3 (6.0%) STAT1 Mutation Categories 1.0001 No change 5 (22.7%) 7 (25.0%) 12 (24.0%) Up regulated 17 (77.3%) 21 (75.0%) 38 (76.0%) TMEM150B Mutation Categories 0.0291 No change 1 (4.5%) 9 (32.1%) 10 (20.0%) Up regulated 21 (95.5%) 19 (67.9%) 40 (80.0%) TTC16 Mutation Categories 0.1521 No change 10 (45.5%) 19 (67.9%) 29 (58.0%) Up regulated 12 (54.5%) 9 (32.1%) 21 (42.0%) 1. Fisher’s Exact Test for Count Data Genes Associated with Metastasis Logistic LASSO regression was used to identify genes associated with metastasis. Cross-validation was used to choose the optimal λλ in the LASSO regression and after λλ was fixed, the genes were chosen from the model fit. Further, due to the cross- validation variations, 100 times cross-validation was used, and every time the selected genes were stored in a matrix. Among the 100 times selections, a gene that was chosen 50 times or more was considered predictive of metastasis. There were 19 genes were chosen 50 times or more – CSAG1, UBE2C, ANKRD1, CSMD3, TOP2A, TPX2, KSR2, CSMD2, MMP20, PCSK1, TMEM150B, ACSL1, TSGA10, KIT, RGL3, PLA2G6, ORM1, ORM2, and PLA2R1. CSAG1, UBE2C, ANKRD1, CSMD3, TOP2A, TPX2, KSR2, CSMD2, MMP20, PCSK1, TMEM150B, ACSL1, TSGA10, KIT, RGL3, and PLA2G6 were used to generate the risk score for metastasis. Table 4 summarized the generation of the risk score. Using this Attorney Docket No.07039-2153WO1 / 2022-168 risk score to predict metastasis, the AUC (area under ROC curve) is 97.1% (95% CI: 93.5% to 100%) (Figure 2). A risk score of 9 was as a cut-off to predict metastasis. Patients who had a risk score of 9 or above were considered as having metastasis, while patients who had a risk score 8 or below were considered as not having metastasis. The sensitivity, specificity and overall accuracy for this cut-off were 95.5%, 85.7%, and 90%, respectively. Table 4. Risk score comparison. PMet PNoMet Total (N=22) (N=28) (N=50) p value Risk score for Metastasis (ACSL1, TSGA10, KIT, < 0.0011 CSAG1, UBE2C, ANKRD1, CSMD3, TOP2A, TPX2,
Figure imgf000123_0001
KSR2, CSMD2, MMP20, PCSK1, TMEM150B, RGL3, PLA2G6) Mean (SD) 10.8 (1.4) 6.8 (1.8) 8.6 (2.6) Median 11.0 7.0 8.5 Q1, Q3 10.0, 12.0 6.0, 8.0 7.0, 10.8 Range 8.0 - 14.0 2.0 - 10.0 2.0 - 14.0 Risk score for Metastasis (ACSL1, TSGA10, KIT, < 0.0012 CSAG1, UBE2C, ANKRD1, CSMD3, TOP2A, TPX2, KSR2, CSMD2, MMP20, PCSK1, TMEM150B, RGL3, PLA2G6) 2 0 (0.0%) 1 (3.6%) 1 (2.0%) 4 0 (0.0%) 3 (10.7%) 3 (6.0%) 5 0 (0.0%) 2 (7.1%) 2 (4.0%) 6 0 (0.0%) 4 (14.3%) 4 (8.0%)
Figure imgf000123_0002
Attorney Docket No.07039-2153WO1 / 2022-168 PMet PNoMet Total (N=22) (N=28) (N=50) p value 12 5 (22.7%) 0 (0.0%) 5 (10.0%) 13 1 (4.5%) 0 (0.0%) 1 (2.0%) 14 1 (4.5%) 0 (0.0%) 1 (2.0%) Risk score for OS (HMGCS1, ANK2, LAMA2, 0.5861 CYP2U1, FAM13C, COL25A1, BIRC5, MELK, IFNE, TG, FAT4) Mean (SD) 7.1 (2.1) 6.9 (1.8) 7.0 (2.0) Median 7.0 7.0 7.0 Q1, Q3 6.0, 9.0 5.8, 8.0 6.0, 8.0 Range 2.0 - 10.0 3.0 - 10.0 2.0 - 10.0 1. Kruskal-Wallis rank sum test 2. Fisher’s Exact Test for Count Data Genes Associated with Overall Survival Regularized Cox regression (i.e., glmnet for survival data) was used to identify genes associated with overall survival. A similar modeling strategy was used as described above to identify genes associated with metastatic status. First a 100 cross-validation was done to choose the genes associated with overall survival. Among the 100 cross-validation models, genes that were selected 50 times or more were considered. There were 11 genes selected 50 times or more: BIRC5, MELK, IFNE, HMGCS1, ANK2, LAMA2, CYP2U1, FAM13C, COL25A1, TG, and FAT4. BIRC5, MELK, IFNE, HMGCS1, ANK2, LAMA2, CYP2U1, FAM13C, COL25A1, TG, and FAT4 were used to generate a risk score for overall survival. The risk score for overall survival was not significantly different between metastatic and non-metastatic groups (p=0.586, Table 4). The risk score based on these genes stratified the patients very well for their overall survival (Figures 3-5 and Table 5). The median survival time for patients with risk score ≤ 4 was 8.9 years, median survival time for patients with risk score between 5 and Attorney Docket No.07039-2153WO1 / 2022-168 7 was 3.9 years and for patients with risk score 8 and above was 1.6 years. With every risk score increase, the risk of death increased by 2.47 (HR: 2.47, 95% CI: 1.64 to 3.74, p<.001) after adjusting for age, immunosuppressant use, and metastasis status. Table 5. Multivariable Cox regression model summary.
Figure imgf000125_0001
Together these results demonstrate that the molecular signature of a cSCC can be used to predict the patient outcome, and can be used to select a treatment based on the predicted outcome(s). For example, an altered level of a CSAG1 polypeptide (or mRNA encoding a CSAG1 polypeptide), an altered level of an UBE2C polypeptide (or mRNA encoding an UBE2C polypeptide), an altered level of an ANKRD1 polypeptide (or mRNA encoding an ANKRD1 polypeptide), an altered level of a CSMD3 polypeptide (or mRNA encoding a CSMD3 polypeptide), an altered level of a TOP2A polypeptide (or mRNA encoding a TOP2A polypeptide), an altered level of a TPX2 polypeptide (or mRNA encoding a TPX2 polypeptide), an altered level of a KSR2 polypeptide (or mRNA encoding a KSR2 polypeptide), an altered level of a CSMD2 polypeptide (or mRNA encoding a CSMD2 polypeptide), an altered level of a MMP20 polypeptide (or mRNA encoding a MMP20 polypeptide), an altered level of a PCSK1 polypeptide (or mRNA encoding a PCSK1 polypeptide), an altered level of a TMEM150B polypeptide (or mRNA encoding a TMEM150B polypeptide), an altered level of an ACSL1 polypeptide (or mRNA encoding an ACSL1 polypeptide), an altered level of a TSGA10 polypeptide (or mRNA encoding a TSGA10 polypeptide), an altered level of a KIT polypeptide (or mRNA encoding a KIT Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide), an altered level of a RGL3 polypeptide (or mRNA encoding a RGL3 polypeptide), and/or an altered level of a PLA2G6 polypeptide (or mRNA encoding a PLA2G6 polypeptide), in a cancer cells of a mammal (e.g., a human) having a cSCC can be used to identify that cSCC as being likely to metastasize (e.g., likely to metastasize to one or more lymph nodes). In another example, an altered level of a BIRC5 polypeptide (or mRNA encoding a BIRC5 polypeptide), an altered level of a MELK polypeptide (or mRNA encoding a MELK polypeptide), an altered level of an IFNE polypeptide (or mRNA encoding an IFNE polypeptide), an altered level of a HMGCS1 polypeptide (or mRNA encoding a HMGCS1 polypeptide), an altered level of an ANK2 polypeptide (or mRNA encoding an ANK2 polypeptide), an altered level of a LAMA2 polypeptide (or mRNA encoding a LAMA2 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a FAM13C polypeptide (or mRNA encoding a FAM13C polypeptide), an altered level of a COL25A1 polypeptide (or mRNA encoding a COL25A1 polypeptide), an altered level of a TG polypeptide (or mRNA encoding a TG polypeptide), and/or an altered level of a FAT4 polypeptide (or mRNA encoding a FAT4 polypeptide), in a cancer cells of a mammal (e.g., a human) having a cSCC can be used to identify that mammal as being likely to experience improved survival (e.g., overall survival). Example 3: cSCC RNA analysis This analysis looked at the differential expression levels of genes to determine a molecular signature between metastatic and non-metastatic samples, with a total of 186 samples from 183 subjects (3 subjects provided 2 samples each). The results in this Example re-present and expand on at least some of the results provided in other Examples. Figure 6 shows the differential gene expression of the 186 samples studied. The genes included are predictive of outcome including metastasis and survival. Differences were seen between metastatic and non-metastatic tumors across these genes of interest. Attorney Docket No.07039-2153WO1 / 2022-168 Patient Population Table 6 shows the patients’ demographics and clinical characteristics of the metastatic (Met) group compared to non-metastatic (No Met) group. There was no significant difference in terms of sex and immunosuppressant use between the two groups. Table 7 shows the tumor characteristic by metastatic (Met) group compared to non- metastatic (No Met) group. There was no significant difference in terms of age at biopsy and tumor stage between the two groups (although the tumor stage was only available for the internal samples). Table 6. Demographics by Group PMet (N=62) PNoMet (N=121) Total (N=183) p value Sex 0.4201 Female 21 (33.9%) 34 (28.1%) 55 (30.1%) Male 41 (66.1%) 87 (71.9%) 128 (69.9%) Immunosuppressant Use 0.1121 No 42 (67.7%) 95 (78.5%) 137 (74.9%) Yes 20 (32.3%) 26 (21.5%) 46 (25.1%) Sample source 0.7421 External 18 (29.0%) 38 (31.4%) 56 (30.6%) Internal 44 (71.0%) 83 (68.6%) 127 (69.4%) 1. Pearson’s Chi-squared test Table 7. Tumor characteristics by Group PMet (N=63) PNoMet (N=123) Total (N=186) p value Tumor.stage 0.0691 N-Miss 18 38 56 T1 1 (2.2%) 0 (0.0%) 1 (0.8%) T2a 25 (55.6%) 57 (67.1%) 82 (63.1%) T2b 15 (33.3%) 27 (31.8%) 42 (32.3%) T3 4 (8.9%) 1 (1.2%) 5 (3.8%) age_cscc 0.5282 Attorney Docket No.07039-2153WO1 / 2022-168 Mean (SD) 76.3 (12.8) 77.5 (11.8) 77.1 (12.1) Median 79.0 80.0 79.0 Q1, Q3 67.5, 85.0 71.0, 85.0 70.0, 85.0 Range 50.0 - 99.0 37.0 - 101.0 37.0 - 101.0 Local recurrence or Metastasis < 0.0011 No 0 (0.0%) 116 (94.3%) 116 (62.4%) Yes 63 (100.0%) 7 (5.7%) 70 (37.6%)
Figure imgf000128_0001
Internal 45 (71.4%) 85 (69.1%) 130 (69.9%) 1. Pearson’s Chi-squared test 2. Linear Model ANOVA Gene summary statistics Table 8 shows the categorical data for each gene including demographics, clinical characteristics, and gene mutations by metastatic status. Table 8. Gene Mutations Comparison between the met and non-met groups PMet (N=63) PNoMet (N=123) Total (N=186) p value ABCA12 Mutation Categories < 0.0011 Down regulated 28 (44.4%) 14 (11.4%) 42 (22.6%) No change 32 (50.8%) 98 (79.7%) 130 (69.9%) Up regulated 3 (4.8%) 11 (8.9%) 14 (7.5%) ABHD5 Mutation Categories < 0.0011 Down regulated 26 (41.3%) 19 (15.4%) 45 (24.2%) No change 35 (55.6%) 83 (67.5%) 118 (63.4%) Up regulated 2 (3.2%) 21 (17.1%) 23 (12.4%) ALOX12 Mutation Categories 0.0091 Down regulated 24 (38.1%) 23 (18.7%) 47 (25.3%) No change 36 (57.1%) 84 (68.3%) 120 (64.5%) Up regulated 3 (4.8%) 16 (13.0%) 19 (10.2%) Attorney Docket No.07039-2153WO1 / 2022-168 ALOX12B Mutation Categories 0.0071 Down regulated 23 (36.5%) 20 (16.3%) 43 (23.1%) No change 35 (55.6%) 84 (68.3%) 119 (64.0%) Up regulated 5 (7.9%) 19 (15.4%) 24 (12.9%) CALCOCO1 Mutation Categories < 0.0011 Down regulated 24 (38.1%) 16 (13.0%) 40 (21.5%) No change 37 (58.7%) 91 (74.0%) 128 (68.8%) Up regulated 2 (3.2%) 16 (13.0%) 18 (9.7%) CASP14 Mutation Categories < 0.0011 Down regulated 21 (33.3%) 14 (11.4%) 35 (18.8%) No change 40 (63.5%) 87 (70.7%) 127 (68.3%) Up regulated 2 (3.2%) 22 (17.9%) 24 (12.9%) CERS3 Mutation Categories < 0.0011 Down regulated 23 (36.5%) 18 (14.6%) 41 (22.0%) No change 40 (63.5%) 92 (74.8%) 132 (71.0%) Up regulated 0 (0.0%) 13 (10.6%) 13 (7.0%) CYP2E1 Mutation Categories 0.0021 Down regulated 24 (38.1%) 20 (16.3%) 44 (23.7%) No change 35 (55.6%) 81 (65.9%) 116 (62.4%) Up regulated 4 (6.3%) 22 (17.9%) 26 (14.0%) CYP3A5 Mutation Categories 0.0311 Down regulated 17 (27.0%) 21 (17.1%) 38 (20.4%) No change 42 (66.7%) 78 (63.4%) 120 (64.5%) Up regulated 4 (6.3%) 24 (19.5%) 28 (15.1%) CYP4F2 Mutation Categories 0.0531 Down regulated 19 (30.2%) 20 (16.3%) 39 (21.0%) No change 39 (61.9%) 83 (67.5%) 122 (65.6%) Up regulated 5 (7.9%) 20 (16.3%) 25 (13.4%) CYP4F22 Mutation Categories < 0.0011 Down regulated 32 (50.8%) 26 (21.1%) 58 (31.2%) No change 29 (46.0%) 82 (66.7%) 111 (59.7%) Up regulated 2 (3.2%) 15 (12.2%) 17 (9.1%) CYP4F3 Mutation Categories < 0.0011 Attorney Docket No.07039-2153WO1 / 2022-168 Down regulated 29 (46.0%) 16 (13.0%) 45 (24.2%) No change 30 (47.6%) 91 (74.0%) 121 (65.1%) Up regulated 4 (6.3%) 16 (13.0%) 20 (10.8%) DGAT2 Mutation Categories < 0.0011 Down regulated 27 (42.9%) 22 (17.9%) 49 (26.3%) No change 33 (52.4%) 81 (65.9%) 114 (61.3%) Up regulated 3 (4.8%) 20 (16.3%) 23 (12.4%) EVPL Mutation Categories < 0.0011 Down regulated 26 (41.3%) 16 (13.0%) 42 (22.6%) No change 36 (57.1%) 90 (73.2%) 126 (67.7%) Up regulated 1 (1.6%) 17 (13.8%) 18 (9.7%) EXPH5 Mutation Categories 0.0021 Down regulated 20 (31.7%) 13 (10.6%) 33 (17.7%) No change 40 (63.5%) 102 (82.9%) 142 (76.3%) Up regulated 3 (4.8%) 8 (6.5%) 11 (5.9%) FCGBP Mutation Categories 0.9701 Down regulated 11 (17.5%) 20 (16.3%) 31 (16.7%) No change 44 (69.8%) 87 (70.7%) 131 (70.4%) Up regulated 8 (12.7%) 16 (13.0%) 24 (12.9%) KRT1 Mutation Categories < 0.0011 Down regulated 24 (38.1%) 12 (9.8%) 36 (19.4%) No change 36 (57.1%) 100 (81.3%) 136 (73.1%) Up regulated 3 (4.8%) 11 (8.9%) 14 (7.5%) KRT10 Mutation Categories < 0.0011 Down regulated 22 (34.9%) 16 (13.0%) 38 (20.4%) No change 40 (63.5%) 91 (74.0%) 131 (70.4%) Up regulated 1 (1.6%) 16 (13.0%) 17 (9.1%) KRT2 Mutation Categories 0.0011 Down regulated 22 (34.9%) 23 (18.7%) 45 (24.2%) No change 39 (61.9%) 76 (61.8%) 115 (61.8%) Up regulated 2 (3.2%) 24 (19.5%) 26 (14.0%) LCE6A Mutation Categories 0.0011 Down regulated 23 (36.5%) 23 (18.7%) 46 (24.7%) Attorney Docket No.07039-2153WO1 / 2022-168 No change 38 (60.3%) 78 (63.4%) 116 (62.4%) Up regulated 2 (3.2%) 22 (17.9%) 24 (12.9%) NDRG4 Mutation Categories 0.0011 Down regulated 24 (38.1%) 20 (16.3%) 44 (23.7%) No change 36 (57.1%) 84 (68.3%) 120 (64.5%) Up regulated 3 (4.8%) 19 (15.4%) 22 (11.8%) PLA2G2F Mutation Categories < 0.0011 Down regulated 31 (49.2%) 24 (19.5%) 55 (29.6%) No change 28 (44.4%) 80 (65.0%) 108 (58.1%) Up regulated 4 (6.3%) 19 (15.4%) 23 (12.4%) PLA2G4B Mutation Categories < 0.0011 Down regulated 27 (42.9%) 21 (17.1%) 48 (25.8%) No change 35 (55.6%) 89 (72.4%) 124 (66.7%) Up regulated 1 (1.6%) 13 (10.6%) 14 (7.5%) PLA2G4D Mutation Categories < 0.0011 Down regulated 28 (44.4%) 19 (15.4%) 47 (25.3%) No change 32 (50.8%) 87 (70.7%) 119 (64.0%) Up regulated 3 (4.8%) 17 (13.8%) 20 (10.8%) PLA2G4E Mutation Categories 0.0011 Down regulated 21 (33.3%) 14 (11.4%) 35 (18.8%) No change 39 (61.9%) 94 (76.4%) 133 (71.5%) Up regulated 3 (4.8%) 15 (12.2%) 18 (9.7%) PLB1 Mutation Categories 0.0011 Down regulated 19 (30.2%) 16 (13.0%) 35 (18.8%) No change 43 (68.3%) 91 (74.0%) 134 (72.0%) Up regulated 1 (1.6%) 16 (13.0%) 17 (9.1%) PPL Mutation Categories 0.0471 Down regulated 20 (31.7%) 20 (16.3%) 40 (21.5%) No change 38 (60.3%) 86 (69.9%) 124 (66.7%) Up regulated 5 (7.9%) 17 (13.8%) 22 (11.8%) ZNF750 Mutation Categories < 0.0011 Down regulated 27 (42.9%) 16 (13.0%) 43 (23.1%) No change 34 (54.0%) 89 (72.4%) 123 (66.1%) Attorney Docket No.07039-2153WO1 / 2022-168 Up regulated 2 (3.2%) 18 (14.6%) 20 (10.8%) ACAT2 Mutation Categories 0.0961 Down regulated 13 (20.6%) 14 (11.4%) 27 (14.5%) No change 46 (73.0%) 91 (74.0%) 137 (73.7%) Up regulated 4 (6.3%) 18 (14.6%) 22 (11.8%) ACSL1 Mutation Categories < 0.0011 Down regulated 19 (30.2%) 15 (12.2%) 34 (18.3%) No change 43 (68.3%) 89 (72.4%) 132 (71.0%) Up regulated 1 (1.6%) 19 (15.4%) 20 (10.8%) ALDH3A2 Mutation Categories < 0.0011 Down regulated 25 (39.7%) 18 (14.6%) 43 (23.1%) No change 33 (52.4%) 82 (66.7%) 115 (61.8%) Up regulated 5 (7.9%) 23 (18.7%) 28 (15.1%) DHCR7 Mutation Categories < 0.0011 Down regulated 21 (33.3%) 16 (13.0%) 37 (19.9%) No change 40 (63.5%) 87 (70.7%) 127 (68.3%) Up regulated 2 (3.2%) 20 (16.3%) 22 (11.8%) FASN Mutation Categories < 0.0011 Down regulated 16 (25.4%) 10 (8.1%) 26 (14.0%) No change 44 (69.8%) 92 (74.8%) 136 (73.1%) Up regulated 3 (4.8%) 21 (17.1%) 24 (12.9%) HMGCR Mutation Categories 0.0011 Down regulated 25 (39.7%) 21 (17.1%) 46 (24.7%) No change 35 (55.6%) 83 (67.5%) 118 (63.4%) Up regulated 3 (4.8%) 19 (15.4%) 22 (11.8%) HMGCS1 Mutation Categories 0.0021 Down regulated 21 (33.3%) 19 (15.4%) 40 (21.5%) No change 40 (63.5%) 85 (69.1%) 125 (67.2%) Up regulated 2 (3.2%) 19 (15.4%) 21 (11.3%) MSMO1 Mutation Categories < 0.0011 Down regulated 24 (38.1%) 19 (15.4%) 43 (23.1%) No change 38 (60.3%) 88 (71.5%) 126 (67.7%) Up regulated 1 (1.6%) 16 (13.0%) 17 (9.1%) Attorney Docket No.07039-2153WO1 / 2022-168 ALDH1A1 Mutation Categories 0.0221 Down regulated 19 (30.2%) 17 (13.8%) 36 (19.4%) No change 39 (61.9%) 88 (71.5%) 127 (68.3%) Up regulated 5 (7.9%) 18 (14.6%) 23 (12.4%) ANK2 Mutation Categories 0.0441 Down regulated 21 (33.3%) 22 (17.9%) 43 (23.1%) No change 35 (55.6%) 77 (62.6%) 112 (60.2%) Up regulated 7 (11.1%) 24 (19.5%) 31 (16.7%) AOX1 Mutation Categories 0.0061 Down regulated 22 (34.9%) 20 (16.3%) 42 (22.6%) No change 38 (60.3%) 85 (69.1%) 123 (66.1%) Up regulated 3 (4.8%) 18 (14.6%) 21 (11.3%) CYP2U1 Mutation Categories 0.1021 Down regulated 7 (11.1%) 19 (15.4%) 26 (14.0%) No change 42 (66.7%) 91 (74.0%) 133 (71.5%) Up regulated 14 (22.2%) 13 (10.6%) 27 (14.5%) EPHX2 Mutation Categories 0.0091 Down regulated 21 (33.3%) 19 (15.4%) 40 (21.5%) No change 38 (60.3%) 84 (68.3%) 122 (65.6%) Up regulated 4 (6.3%) 20 (16.3%) 24 (12.9%) FAM13C Mutation Categories 0.0921 Down regulated 21 (33.3%) 24 (19.5%) 45 (24.2%) No change 37 (58.7%) 81 (65.9%) 118 (63.4%) Up regulated 5 (7.9%) 18 (14.6%) 23 (12.4%) FAT4 Mutation Categories 0.0821 Down regulated 18 (28.6%) 20 (16.3%) 38 (20.4%) No change 41 (65.1%) 86 (69.9%) 127 (68.3%) Up regulated 4 (6.3%) 17 (13.8%) 21 (11.3%) FGF10 Mutation Categories 0.7651 Down regulated 10 (15.9%) 15 (12.2%) 25 (13.4%) No change 46 (73.0%) 92 (74.8%) 138 (74.2%) Up regulated 7 (11.1%) 16 (13.0%) 23 (12.4%) KIT Mutation Categories < 0.0011 Attorney Docket No.07039-2153WO1 / 2022-168 Down regulated 24 (38.1%) 19 (15.4%) 43 (23.1%) No change 37 (58.7%) 87 (70.7%) 124 (66.7%) Up regulated 2 (3.2%) 17 (13.8%) 19 (10.2%) LAMA2 Mutation Categories 0.0981 Down regulated 16 (25.4%) 16 (13.0%) 32 (17.2%) No change 41 (65.1%) 89 (72.4%) 130 (69.9%) Up regulated 6 (9.5%) 18 (14.6%) 24 (12.9%) LIPE Mutation Categories 0.7991 Down regulated 11 (17.5%) 17 (13.8%) 28 (15.1%) No change 45 (71.4%) 90 (73.2%) 135 (72.6%) Up regulated 7 (11.1%) 16 (13.0%) 23 (12.4%) PCSK1 Mutation Categories 0.6731 Down regulated 10 (15.9%) 21 (17.1%) 31 (16.7%) No change 48 (76.2%) 87 (70.7%) 135 (72.6%) Up regulated 5 (7.9%) 15 (12.2%) 20 (10.8%) PLA2G6 Mutation Categories 0.2261 Down regulated 17 (27.0%) 20 (16.3%) 37 (19.9%) No change 39 (61.9%) 88 (71.5%) 127 (68.3%) Up regulated 7 (11.1%) 15 (12.2%) 22 (11.8%) PPARG Mutation Categories 0.0111 Down regulated 19 (30.2%) 19 (15.4%) 38 (20.4%) No change 40 (63.5%) 81 (65.9%) 121 (65.1%) Up regulated 4 (6.3%) 23 (18.7%) 27 (14.5%) RGL3 Mutation Categories 0.4461 Down regulated 15 (23.8%) 20 (16.3%) 35 (18.8%) No change 42 (66.7%) 88 (71.5%) 130 (69.9%) Up regulated 6 (9.5%) 15 (12.2%) 21 (11.3%) RYR2 Mutation Categories 0.1321 Down regulated 17 (27.0%) 20 (16.3%) 37 (19.9%) No change 40 (63.5%) 82 (66.7%) 122 (65.6%) Up regulated 6 (9.5%) 21 (17.1%) 27 (14.5%) SCARA5 Mutation Categories 0.1511 Down regulated 15 (23.8%) 23 (18.7%) 38 (20.4%) Attorney Docket No.07039-2153WO1 / 2022-168 No change 42 (66.7%) 75 (61.0%) 117 (62.9%) Up regulated 6 (9.5%) 25 (20.3%) 31 (16.7%) SVEP1 Mutation Categories 0.0691 Down regulated 21 (33.3%) 23 (18.7%) 44 (23.7%) No change 36 (57.1%) 80 (65.0%) 116 (62.4%) Up regulated 6 (9.5%) 20 (16.3%) 26 (14.0%) SYNE1 Mutation Categories 0.8471 Down regulated 8 (12.7%) 13 (10.6%) 21 (11.3%) No change 45 (71.4%) 92 (74.8%) 137 (73.7%) Up regulated 10 (15.9%) 18 (14.6%) 28 (15.1%) TRPM1 Mutation Categories 0.0041 Down regulated 18 (28.6%) 18 (14.6%) 36 (19.4%) No change 43 (68.3%) 84 (68.3%) 127 (68.3%) Up regulated 2 (3.2%) 21 (17.1%) 23 (12.4%) TSGA10 Mutation Categories 0.3621 Down regulated 14 (22.2%) 18 (14.6%) 32 (17.2%) No change 44 (69.8%) 90 (73.2%) 134 (72.0%) Up regulated 5 (7.9%) 15 (12.2%) 20 (10.8%) BIRC5 Mutation Categories 0.0031 Down regulated 2 (3.2%) 22 (17.9%) 24 (12.9%) No change 39 (61.9%) 77 (62.6%) 116 (62.4%) Up regulated 22 (34.9%) 24 (19.5%) 46 (24.7%) BUB1 Mutation Categories 0.0231 Down regulated 2 (3.2%) 20 (16.3%) 22 (11.8%) No change 47 (74.6%) 82 (66.7%) 129 (69.4%) Up regulated 14 (22.2%) 21 (17.1%) 35 (18.8%) CCNA2 Mutation Categories 0.0281 Down regulated 4 (6.3%) 18 (14.6%) 22 (11.8%) No change 39 (61.9%) 85 (69.1%) 124 (66.7%) Up regulated 20 (31.7%) 20 (16.3%) 40 (21.5%) CCNB1 Mutation Categories 0.7521 Down regulated 8 (12.7%) 19 (15.4%) 27 (14.5%) No change 42 (66.7%) 84 (68.3%) 126 (67.7%) Attorney Docket No.07039-2153WO1 / 2022-168 Up regulated 13 (20.6%) 20 (16.3%) 33 (17.7%) CDC20 Mutation Categories 0.0511 Down regulated 3 (4.8%) 21 (17.1%) 24 (12.9%) No change 47 (74.6%) 81 (65.9%) 128 (68.8%) Up regulated 13 (20.6%) 21 (17.1%) 34 (18.3%) CDCA5 Mutation Categories 0.0451 Down regulated 3 (4.8%) 15 (12.2%) 18 (9.7%) No change 43 (68.3%) 91 (74.0%) 134 (72.0%) Up regulated 17 (27.0%) 17 (13.8%) 34 (18.3%) CDKN2A Mutation Categories 0.3201 Down regulated 9 (14.3%) 18 (14.6%) 27 (14.5%) No change 38 (60.3%) 85 (69.1%) 123 (66.1%) Up regulated 16 (25.4%) 20 (16.3%) 36 (19.4%) CENPF Mutation Categories < 0.0011 Down regulated 0 (0.0%) 19 (15.4%) 19 (10.2%) No change 43 (68.3%) 81 (65.9%) 124 (66.7%) Up regulated 20 (31.7%) 23 (18.7%) 43 (23.1%) CEP55 Mutation Categories 0.0031 Down regulated 1 (1.6%) 19 (15.4%) 20 (10.8%) No change 42 (66.7%) 80 (65.0%) 122 (65.6%) Up regulated 20 (31.7%) 24 (19.5%) 44 (23.7%) COL22A1 Mutation Categories 0.0781 Down regulated 8 (12.7%) 16 (13.0%) 24 (12.9%) No change 34 (54.0%) 84 (68.3%) 118 (63.4%) Up regulated 21 (33.3%) 23 (18.7%) 44 (23.7%) CXCL10 Mutation Categories 0.1211 Down regulated 8 (12.7%) 18 (14.6%) 26 (14.0%) No change 37 (58.7%) 86 (69.9%) 123 (66.1%) Up regulated 18 (28.6%) 19 (15.4%) 37 (19.9%) CXCL8 Mutation Categories 0.2141 Down regulated 5 (7.9%) 21 (17.1%) 26 (14.0%) No change 45 (71.4%) 82 (66.7%) 127 (68.3%) Up regulated 13 (20.6%) 20 (16.3%) 33 (17.7%) Attorney Docket No.07039-2153WO1 / 2022-168 DLGAP5 Mutation Categories 0.0891 Down regulated 2 (3.2%) 14 (11.4%) 16 (8.6%) No change 45 (71.4%) 88 (71.5%) 133 (71.5%) Up regulated 16 (25.4%) 21 (17.1%) 37 (19.9%) FOXM1 Mutation Categories 0.0121 Down regulated 3 (4.8%) 19 (15.4%) 22 (11.8%) No change 36 (57.1%) 78 (63.4%) 114 (61.3%) Up regulated 24 (38.1%) 26 (21.1%) 50 (26.9%) MUC16 Mutation Categories 0.2061 Down regulated 8 (12.7%) 15 (12.2%) 23 (12.4%) No change 38 (60.3%) 88 (71.5%) 126 (67.7%) Up regulated 17 (27.0%) 20 (16.3%) 37 (19.9%) NUSAP1 Mutation Categories 0.0151 Down regulated 2 (3.2%) 20 (16.3%) 22 (11.8%) No change 45 (71.4%) 82 (66.7%) 127 (68.3%) Up regulated 16 (25.4%) 21 (17.1%) 37 (19.9%) PLK1 Mutation Categories 0.1941 Down regulated 4 (6.3%) 18 (14.6%) 22 (11.8%) No change 44 (69.8%) 83 (67.5%) 127 (68.3%) Up regulated 15 (23.8%) 22 (17.9%) 37 (19.9%) RRM2 Mutation Categories 0.0151 Down regulated 4 (6.3%) 19 (15.4%) 23 (12.4%) No change 38 (60.3%) 84 (68.3%) 122 (65.6%) Up regulated 21 (33.3%) 20 (16.3%) 41 (22.0%) SMC4 Mutation Categories 0.0091 Down regulated 1 (1.6%) 15 (12.2%) 16 (8.6%) No change 42 (66.7%) 86 (69.9%) 128 (68.8%) Up regulated 20 (31.7%) 22 (17.9%) 42 (22.6%) STAT1 Mutation Categories 0.0161 Down regulated 13 (20.6%) 18 (14.6%) 31 (16.7%) No change 31 (49.2%) 86 (69.9%) 117 (62.9%) Up regulated 19 (30.2%) 19 (15.4%) 38 (20.4%) TNFRSF21 Mutation Categories 0.1341 Attorney Docket No.07039-2153WO1 / 2022-168 Down regulated 19 (30.2%) 24 (19.5%) 43 (23.1%) No change 30 (47.6%) 77 (62.6%) 107 (57.5%) Up regulated 14 (22.2%) 22 (17.9%) 36 (19.4%) TOP2A Mutation Categories 0.0111 Down regulated 2 (3.2%) 20 (16.3%) 22 (11.8%) No change 44 (69.8%) 83 (67.5%) 127 (68.3%) Up regulated 17 (27.0%) 20 (16.3%) 37 (19.9%) UBE2C Mutation Categories 0.0091 Down regulated 1 (1.6%) 19 (15.4%) 20 (10.8%) No change 47 (74.6%) 79 (64.2%) 126 (67.7%) Up regulated 15 (23.8%) 25 (20.3%) 40 (21.5%) ASPM Mutation Categories 0.0221 Down regulated 5 (7.9%) 14 (11.4%) 19 (10.2%) No change 37 (58.7%) 90 (73.2%) 127 (68.3%) Up regulated 21 (33.3%) 19 (15.4%) 40 (21.5%) AURKA Mutation Categories 0.5361 Down regulated 6 (9.5%) 13 (10.6%) 19 (10.2%) No change 46 (73.0%) 96 (78.0%) 142 (76.3%) Up regulated 11 (17.5%) 14 (11.4%) 25 (13.4%) AURKB Mutation Categories 0.0051 Down regulated 3 (4.8%) 16 (13.0%) 19 (10.2%) No change 38 (60.3%) 88 (71.5%) 126 (67.7%) Up regulated 22 (34.9%) 19 (15.4%) 41 (22.0%) BUB1B Mutation Categories 0.1321 Down regulated 3 (4.8%) 14 (11.4%) 17 (9.1%) No change 42 (66.7%) 87 (70.7%) 129 (69.4%) Up regulated 18 (28.6%) 22 (17.9%) 40 (21.5%) CCNB2 Mutation Categories 0.0081 Down regulated 3 (4.8%) 10 (8.1%) 13 (7.0%) No change 39 (61.9%) 96 (78.0%) 135 (72.6%) Up regulated 21 (33.3%) 17 (13.8%) 38 (20.4%) CDC25C Mutation Categories 0.6321 Down regulated 8 (12.7%) 22 (17.9%) 30 (16.1%) Attorney Docket No.07039-2153WO1 / 2022-168 No change 42 (66.7%) 80 (65.0%) 122 (65.6%) Up regulated 13 (20.6%) 21 (17.1%) 34 (18.3%) CDC6 Mutation Categories < 0.0011 Down regulated 2 (3.2%) 18 (14.6%) 20 (10.8%) No change 38 (60.3%) 86 (69.9%) 124 (66.7%) Up regulated 23 (36.5%) 19 (15.4%) 42 (22.6%) CDCA8 Mutation Categories 0.7071 Down regulated 7 (11.1%) 12 (9.8%) 19 (10.2%) No change 42 (66.7%) 89 (72.4%) 131 (70.4%) Up regulated 14 (22.2%) 22 (17.9%) 36 (19.4%) CDK1 Mutation Categories < 0.0011 Down regulated 1 (1.6%) 15 (12.2%) 16 (8.6%) No change 37 (58.7%) 88 (71.5%) 125 (67.2%) Up regulated 25 (39.7%) 20 (16.3%) 45 (24.2%) CENPE Mutation Categories 0.0871 Down regulated 5 (7.9%) 17 (13.8%) 22 (11.8%) No change 45 (71.4%) 94 (76.4%) 139 (74.7%) Up regulated 13 (20.6%) 12 (9.8%) 25 (13.4%) CHEK1 Mutation Categories 0.1631 Down regulated 2 (3.2%) 12 (9.8%) 14 (7.5%) No change 47 (74.6%) 93 (75.6%) 140 (75.3%) Up regulated 14 (22.2%) 18 (14.6%) 32 (17.2%) HJURP Mutation Categories 0.0311 Down regulated 3 (4.8%) 15 (12.2%) 18 (9.7%) No change 43 (68.3%) 92 (74.8%) 135 (72.6%) Up regulated 17 (27.0%) 16 (13.0%) 33 (17.7%) IL1B Mutation Categories 0.3831 Down regulated 8 (12.7%) 17 (13.8%) 25 (13.4%) No change 40 (63.5%) 87 (70.7%) 127 (68.3%) Up regulated 15 (23.8%) 19 (15.4%) 34 (18.3%) KIF11 Mutation Categories 0.0041 Down regulated 2 (3.2%) 11 (8.9%) 13 (7.0%) No change 39 (61.9%) 94 (76.4%) 133 (71.5%) Attorney Docket No.07039-2153WO1 / 2022-168 Up regulated 22 (34.9%) 18 (14.6%) 40 (21.5%) KIF20A Mutation Categories 0.0581 Down regulated 8 (12.7%) 18 (14.6%) 26 (14.0%) No change 37 (58.7%) 88 (71.5%) 125 (67.2%) Up regulated 18 (28.6%) 17 (13.8%) 35 (18.8%) KIF23 Mutation Categories 0.0391 Down regulated 3 (4.8%) 14 (11.4%) 17 (9.1%) No change 41 (65.1%) 90 (73.2%) 131 (70.4%) Up regulated 19 (30.2%) 19 (15.4%) 38 (20.4%) KIF2C Mutation Categories 0.0211 Down regulated 3 (4.8%) 19 (15.4%) 22 (11.8%) No change 40 (63.5%) 82 (66.7%) 122 (65.6%) Up regulated 20 (31.7%) 22 (17.9%) 42 (22.6%) KIF4A Mutation Categories 0.1881 Down regulated 4 (6.3%) 16 (13.0%) 20 (10.8%) No change 43 (68.3%) 87 (70.7%) 130 (69.9%) Up regulated 16 (25.4%) 20 (16.3%) 36 (19.4%) MAD2L1 Mutation Categories 0.0021 Down regulated 5 (7.9%) 8 (6.5%) 13 (7.0%) No change 37 (58.7%) 100 (81.3%) 137 (73.7%) Up regulated 21 (33.3%) 15 (12.2%) 36 (19.4%) MELK Mutation Categories 0.0061 Down regulated 4 (6.3%) 13 (10.6%) 17 (9.1%) No change 39 (61.9%) 95 (77.2%) 134 (72.0%) Up regulated 20 (31.7%) 15 (12.2%) 35 (18.8%) MKI67 Mutation Categories 0.0041 Down regulated 1 (1.6%) 16 (13.0%) 17 (9.1%) No change 40 (63.5%) 84 (68.3%) 124 (66.7%) Up regulated 22 (34.9%) 23 (18.7%) 45 (24.2%) NCAPG Mutation Categories 0.0101 Down regulated 4 (6.3%) 9 (7.3%) 13 (7.0%) No change 39 (61.9%) 98 (79.7%) 137 (73.7%) Up regulated 20 (31.7%) 16 (13.0%) 36 (19.4%) Attorney Docket No.07039-2153WO1 / 2022-168 NCAPH Mutation Categories 0.1411 Down regulated 4 (6.3%) 11 (8.9%) 15 (8.1%) No change 43 (68.3%) 95 (77.2%) 138 (74.2%) Up regulated 16 (25.4%) 17 (13.8%) 33 (17.7%) NDC80 Mutation Categories 0.0281 Down regulated 6 (9.5%) 16 (13.0%) 22 (11.8%) No change 37 (58.7%) 89 (72.4%) 126 (67.7%) Up regulated 20 (31.7%) 18 (14.6%) 38 (20.4%) NQO1 Mutation Categories 0.0621 Down regulated 13 (20.6%) 16 (13.0%) 29 (15.6%) No change 36 (57.1%) 91 (74.0%) 127 (68.3%) Up regulated 14 (22.2%) 16 (13.0%) 30 (16.1%) NUF2 Mutation Categories 0.0671 Down regulated 6 (9.5%) 18 (14.6%) 24 (12.9%) No change 39 (61.9%) 87 (70.7%) 126 (67.7%) Up regulated 18 (28.6%) 18 (14.6%) 36 (19.4%) PBK Mutation Categories 0.5671 Down regulated 7 (11.1%) 21 (17.1%) 28 (15.1%) No change 44 (69.8%) 82 (66.7%) 126 (67.7%) Up regulated 12 (19.0%) 20 (16.3%) 32 (17.2%) PRC1 Mutation Categories 0.1111 Down regulated 10 (15.9%) 15 (12.2%) 25 (13.4%) No change 37 (58.7%) 90 (73.2%) 127 (68.3%) Up regulated 16 (25.4%) 18 (14.6%) 34 (18.3%) PTTG1 Mutation Categories 0.0261 Down regulated 9 (14.3%) 20 (16.3%) 29 (15.6%) No change 34 (54.0%) 85 (69.1%) 119 (64.0%) Up regulated 20 (31.7%) 18 (14.6%) 38 (20.4%) TPX2 Mutation Categories 0.1831 Down regulated 2 (3.2%) 11 (8.9%) 13 (7.0%) No change 48 (76.2%) 96 (78.0%) 144 (77.4%) Up regulated 13 (20.6%) 16 (13.0%) 29 (15.6%) TTK Mutation Categories 0.0531 Attorney Docket No.07039-2153WO1 / 2022-168 Down regulated 6 (9.5%) 10 (8.1%) 16 (8.6%) No change 40 (63.5%) 97 (78.9%) 137 (73.7%) Up regulated 17 (27.0%) 16 (13.0%) 33 (17.7%) COL11A1 Mutation Categories 0.1241 Down regulated 7 (11.1%) 17 (13.8%) 24 (12.9%) No change 37 (58.7%) 85 (69.1%) 122 (65.6%) Up regulated 19 (30.2%) 21 (17.1%) 40 (21.5%) CSMD2 Mutation Categories 0.4351 Down regulated 8 (12.7%) 20 (16.3%) 28 (15.1%) No change 39 (61.9%) 81 (65.9%) 120 (64.5%) Up regulated 16 (25.4%) 22 (17.9%) 38 (20.4%) DGKI Mutation Categories 0.1531 Down regulated 10 (15.9%) 18 (14.6%) 28 (15.1%) No change 38 (60.3%) 89 (72.4%) 127 (68.3%) Up regulated 15 (23.8%) 16 (13.0%) 31 (16.7%) FN1 Mutation Categories < 0.0011 Down regulated 2 (3.2%) 17 (13.8%) 19 (10.2%) No change 34 (54.0%) 86 (69.9%) 120 (64.5%) Up regulated 27 (42.9%) 20 (16.3%) 47 (25.3%) IFNE Mutation Categories 0.2481 Down regulated 9 (14.3%) 23 (18.7%) 32 (17.2%) No change 38 (60.3%) 81 (65.9%) 119 (64.0%) Up regulated 16 (25.4%) 19 (15.4%) 35 (18.8%) ITGA5 Mutation Categories 0.0031 Down regulated 4 (6.3%) 18 (14.6%) 22 (11.8%) No change 37 (58.7%) 88 (71.5%) 125 (67.2%) Up regulated 22 (34.9%) 17 (13.8%) 39 (21.0%) ZNF469 Mutation Categories 0.0491 Down regulated 7 (11.1%) 15 (12.2%) 22 (11.8%) No change 36 (57.1%) 88 (71.5%) 124 (66.7%) Up regulated 20 (31.7%) 20 (16.3%) 40 (21.5%) ABCB11 Mutation Categories 0.7481 Down regulated 11 (17.5%) 17 (13.8%) 28 (15.1%) Attorney Docket No.07039-2153WO1 / 2022-168 No change 46 (73.0%) 95 (77.2%) 141 (75.8%) Up regulated 6 (9.5%) 11 (8.9%) 17 (9.1%) ALOX15 Mutation Categories 0.1121 Down regulated 12 (19.0%) 18 (14.6%) 30 (16.1%) No change 48 (76.2%) 87 (70.7%) 135 (72.6%) Up regulated 3 (4.8%) 18 (14.6%) 21 (11.3%) APOB Mutation Categories 0.7991 Down regulated 11 (17.5%) 17 (13.8%) 28 (15.1%) No change 47 (74.6%) 95 (77.2%) 142 (76.3%) Up regulated 5 (7.9%) 11 (8.9%) 16 (8.6%) CSAG1_ISP Mutation Categories 0.2291 Down regulated 14 (22.2%) 18 (14.6%) 32 (17.2%) No change 37 (58.7%) 87 (70.7%) 124 (66.7%) Up regulated 12 (19.0%) 18 (14.6%) 30 (16.1%) CSMD1 Mutation Categories 0.5241 Down regulated 15 (23.8%) 21 (17.1%) 36 (19.4%) No change 38 (60.3%) 83 (67.5%) 121 (65.1%) Up regulated 10 (15.9%) 19 (15.4%) 29 (15.6%) CYP1A1 Mutation Categories 0.3191 Down regulated 13 (20.6%) 15 (12.2%) 28 (15.1%) No change 43 (68.3%) 91 (74.0%) 134 (72.0%) Up regulated 7 (11.1%) 17 (13.8%) 24 (12.9%) CYP2C9 Mutation Categories 0.7521 Down regulated 13 (20.6%) 20 (16.3%) 33 (17.7%) No change 42 (66.7%) 84 (68.3%) 126 (67.7%) Up regulated 8 (12.7%) 19 (15.4%) 27 (14.5%) CYP4A11 Mutation Categories 0.7181 Down regulated 13 (20.6%) 20 (16.3%) 33 (17.7%) No change 40 (63.5%) 84 (68.3%) 124 (66.7%) Up regulated 10 (15.9%) 19 (15.4%) 29 (15.6%) DNAH3 Mutation Categories 0.5431 Down regulated 13 (20.6%) 18 (14.6%) 31 (16.7%) No change 42 (66.7%) 89 (72.4%) 131 (70.4%) Attorney Docket No.07039-2153WO1 / 2022-168 Up regulated 8 (12.7%) 16 (13.0%) 24 (12.9%) FAM178B Mutation Categories 0.2661 Down regulated 14 (22.2%) 18 (14.6%) 32 (17.2%) No change 43 (68.3%) 85 (69.1%) 128 (68.8%) Up regulated 6 (9.5%) 20 (16.3%) 26 (14.0%) FAM81B Mutation Categories 0.8161 Down regulated 12 (19.0%) 19 (15.4%) 31 (16.7%) No change 42 (66.7%) 86 (69.9%) 128 (68.8%) Up regulated 9 (14.3%) 18 (14.6%) 27 (14.5%) KRTAP5 Mutation Categories 1.0001 Down regulated 5 (7.9%) 9 (7.3%) 14 (7.5%) No change 51 (81.0%) 100 (81.3%) 151 (81.2%) Up regulated 7 (11.1%) 14 (11.4%) 21 (11.3%) MGAM Mutation Categories 0.2541 Down regulated 11 (17.5%) 23 (18.7%) 34 (18.3%) No change 39 (61.9%) 86 (69.9%) 125 (67.2%) Up regulated 13 (20.6%) 14 (11.4%) 27 (14.5%) MMP20 Mutation Categories 0.6061 Down regulated 13 (20.6%) 19 (15.4%) 32 (17.2%) No change 42 (66.7%) 90 (73.2%) 132 (71.0%) Up regulated 8 (12.7%) 14 (11.4%) 22 (11.8%) POTEM Mutation Categories 0.1781 Down regulated 5 (7.9%) 9 (7.3%) 14 (7.5%) No change 42 (66.7%) 96 (78.0%) 138 (74.2%) Up regulated 16 (25.4%) 18 (14.6%) 34 (18.3%) RHAG Mutation Categories 0.2391 Down regulated 13 (20.6%) 18 (14.6%) 31 (16.7%) No change 41 (65.1%) 94 (76.4%) 135 (72.6%) Up regulated 9 (14.3%) 11 (8.9%) 20 (10.8%) SLITRK3 Mutation Categories 0.2871 Down regulated 11 (17.5%) 15 (12.2%) 26 (14.0%) No change 49 (77.8%) 95 (77.2%) 144 (77.4%) Up regulated 3 (4.8%) 13 (10.6%) 16 (8.6%) Attorney Docket No.07039-2153WO1 / 2022-168 TG Mutation Categories 0.2781 Down regulated 14 (22.2%) 17 (13.8%) 31 (16.7%) No change 43 (68.3%) 89 (72.4%) 132 (71.0%) Up regulated 6 (9.5%) 17 (13.8%) 23 (12.4%) TNNI1 Mutation Categories 0.4381 Down regulated 13 (20.6%) 17 (13.8%) 30 (16.1%) No change 47 (74.6%) 97 (78.9%) 144 (77.4%) Up regulated 3 (4.8%) 9 (7.3%) 12 (6.5%) USH2A Mutation Categories 0.7811 Down regulated 13 (20.6%) 20 (16.3%) 33 (17.7%) No change 40 (63.5%) 83 (67.5%) 123 (66.1%) Up regulated 10 (15.9%) 20 (16.3%) 30 (16.1%) ACTA1 Mutation Categories 0.6561 Down regulated 2 (3.2%) 2 (1.6%) 4 (2.2%) No change 53 (84.1%) 101 (82.1%) 154 (82.8%) Up regulated 8 (12.7%) 20 (16.3%) 28 (15.1%) ACTN2 Mutation Categories 0.7521 Down regulated 2 (3.2%) 2 (1.6%) 4 (2.2%) No change 53 (84.1%) 103 (83.7%) 156 (83.9%) Up regulated 8 (12.7%) 18 (14.6%) 26 (14.0%) ANKRD1 Mutation Categories 0.6791 Down regulated 8 (12.7%) 11 (8.9%) 19 (10.2%) No change 47 (74.6%) 93 (75.6%) 140 (75.3%) Up regulated 8 (12.7%) 19 (15.4%) 27 (14.5%) CKM Mutation Categories 0.2941 Down regulated 0 (0.0%) 3 (2.4%) 3 (1.6%) No change 56 (88.9%) 99 (80.5%) 155 (83.3%) Up regulated 7 (11.1%) 21 (17.1%) 28 (15.1%) CMYA5 Mutation Categories 0.2641 Down regulated 10 (15.9%) 11 (8.9%) 21 (11.3%) No change 47 (74.6%) 94 (76.4%) 141 (75.8%) Up regulated 6 (9.5%) 18 (14.6%) 24 (12.9%) FCRL5 Mutation Categories 0.2101 Attorney Docket No.07039-2153WO1 / 2022-168 Down regulated 11 (17.5%) 14 (11.4%) 25 (13.4%) No change 36 (57.1%) 86 (69.9%) 122 (65.6%) Up regulated 16 (25.4%) 23 (18.7%) 39 (21.0%) HMGCS2 Mutation Categories 0.1111 Down regulated 16 (25.4%) 20 (16.3%) 36 (19.4%) No change 41 (65.1%) 79 (64.2%) 120 (64.5%) Up regulated 6 (9.5%) 24 (19.5%) 30 (16.1%) HSPB7 Mutation Categories 0.4781 Down regulated 8 (12.7%) 10 (8.1%) 18 (9.7%) No change 49 (77.8%) 96 (78.0%) 145 (78.0%) Up regulated 6 (9.5%) 17 (13.8%) 23 (12.4%) KRT28 Mutation Categories 0.8051 Down regulated 3 (4.8%) 7 (5.7%) 10 (5.4%) No change 55 (87.3%) 102 (82.9%) 157 (84.4%) Up regulated 5 (7.9%) 14 (11.4%) 19 (10.2%) MUC5B Mutation Categories 0.9131 Down regulated 3 (4.8%) 6 (4.9%) 9 (4.8%) No change 57 (90.5%) 113 (91.9%) 170 (91.4%) Up regulated 3 (4.8%) 4 (3.3%) 7 (3.8%) SMPX Mutation Categories 0.2441 Down regulated 5 (7.9%) 7 (5.7%) 12 (6.5%) No change 55 (87.3%) 101 (82.1%) 156 (83.9%) Up regulated 3 (4.8%) 15 (12.2%) 18 (9.7%) SYNPO2L Mutation Categories 0.2911 Down regulated 8 (12.7%) 12 (9.8%) 20 (10.8%) No change 51 (81.0%) 94 (76.4%) 145 (78.0%) Up regulated 4 (6.3%) 17 (13.8%) 21 (11.3%) TTN Mutation Categories 0.0781 Down regulated 13 (20.6%) 11 (8.9%) 24 (12.9%) No change 42 (66.7%) 91 (74.0%) 133 (71.5%) Up regulated 8 (12.7%) 21 (17.1%) 29 (15.6%) XIRP2 Mutation Categories 0.7571 Down regulated 2 (3.2%) 3 (2.4%) 5 (2.7%) Attorney Docket No.07039-2153WO1 / 2022-168 No change 55 (87.3%) 104 (84.6%) 159 (85.5%) Up regulated 6 (9.5%) 16 (13.0%) 22 (11.8%) ALOX15B Mutation Categories 0.0091 Down regulated 21 (33.3%) 24 (19.5%) 45 (24.2%) No change 39 (61.9%) 76 (61.8%) 115 (61.8%) Up regulated 3 (4.8%) 23 (18.7%) 26 (14.0%) DMD Mutation Categories 0.0871 Down regulated 13 (20.6%) 14 (11.4%) 27 (14.5%) No change 45 (71.4%) 88 (71.5%) 133 (71.5%) Up regulated 5 (7.9%) 21 (17.1%) 26 (14.0%) FA2H Mutation Categories 0.1441 Down regulated 15 (23.8%) 18 (14.6%) 33 (17.7%) No change 41 (65.1%) 80 (65.0%) 121 (65.1%) Up regulated 7 (11.1%) 25 (20.3%) 32 (17.2%) FADS1 Mutation Categories 0.0201 Down regulated 7 (11.1%) 13 (10.6%) 20 (10.8%) No change 53 (84.1%) 86 (69.9%) 139 (74.7%) Up regulated 3 (4.8%) 24 (19.5%) 27 (14.5%) FADS2 Mutation Categories 0.0301 Down regulated 6 (9.5%) 16 (13.0%) 22 (11.8%) No change 53 (84.1%) 83 (67.5%) 136 (73.1%) Up regulated 4 (6.3%) 24 (19.5%) 28 (15.1%) PLA2R1 Mutation Categories 0.0021 Down regulated 20 (31.7%) 13 (10.6%) 33 (17.7%) No change 37 (58.7%) 92 (74.8%) 129 (69.4%) Up regulated 6 (9.5%) 18 (14.6%) 24 (12.9%) TCHH Mutation Categories 0.8451 Down regulated 14 (22.2%) 28 (22.8%) 42 (22.6%) No change 39 (61.9%) 71 (57.7%) 110 (59.1%) Up regulated 10 (15.9%) 24 (19.5%) 34 (18.3%) THRSP Mutation Categories 0.0141 Down regulated 17 (27.0%) 20 (16.3%) 37 (19.9%) No change 41 (65.1%) 74 (60.2%) 115 (61.8%) Attorney Docket No.07039-2153WO1 / 2022-168 Up regulated 5 (7.9%) 29 (23.6%) 34 (18.3%) ARID3C Mutation Categories 0.7631 Down regulated 13 (20.6%) 20 (16.3%) 33 (17.7%) No change 40 (63.5%) 82 (66.7%) 122 (65.6%) Up regulated 10 (15.9%) 21 (17.1%) 31 (16.7%) COL25A1 Mutation Categories 0.7881 Down regulated 13 (20.6%) 20 (16.3%) 33 (17.7%) No change 39 (61.9%) 81 (65.9%) 120 (64.5%) Up regulated 11 (17.5%) 22 (17.9%) 33 (17.7%) CSAG1 Mutation Categories 0.0881 Down regulated 9 (14.3%) 10 (8.1%) 19 (10.2%) No change 44 (69.8%) 103 (83.7%) 147 (79.0%) Up regulated 10 (15.9%) 10 (8.1%) 20 (10.8%) CSMD3 Mutation Categories 0.3191 Down regulated 13 (20.6%) 19 (15.4%) 32 (17.2%) No change 40 (63.5%) 91 (74.0%) 131 (70.4%) Up regulated 10 (15.9%) 13 (10.6%) 23 (12.4%) CYP2C19 Mutation Categories 0.6791 Down regulated 14 (22.2%) 21 (17.1%) 35 (18.8%) No change 39 (61.9%) 79 (64.2%) 118 (63.4%) Up regulated 10 (15.9%) 23 (18.7%) 33 (17.7%) CYP3A4 Mutation Categories 0.4431 Down regulated 14 (22.2%) 19 (15.4%) 33 (17.7%) No change 38 (60.3%) 84 (68.3%) 122 (65.6%) Up regulated 11 (17.5%) 20 (16.3%) 31 (16.7%) CYP4A22 Mutation Categories 0.8331 Down regulated 13 (20.6%) 21 (17.1%) 34 (18.3%) No change 39 (61.9%) 80 (65.0%) 119 (64.0%) Up regulated 11 (17.5%) 22 (17.9%) 33 (17.7%) DLGAP3 Mutation Categories 0.4251 Down regulated 9 (14.3%) 12 (9.8%) 21 (11.3%) No change 50 (79.4%) 97 (78.9%) 147 (79.0%) Up regulated 4 (6.3%) 14 (11.4%) 18 (9.7%) Attorney Docket No.07039-2153WO1 / 2022-168 DNAH5 Mutation Categories 0.1261 Down regulated 11 (17.5%) 16 (13.0%) 27 (14.5%) No change 41 (65.1%) 96 (78.0%) 137 (73.7%) Up regulated 11 (17.5%) 11 (8.9%) 22 (11.8%) DNAJC5B Mutation Categories 0.4631 Down regulated 14 (22.2%) 20 (16.3%) 34 (18.3%) No change 36 (57.1%) 81 (65.9%) 117 (62.9%) Up regulated 13 (20.6%) 22 (17.9%) 35 (18.8%) GRM8 Mutation Categories 0.4751 Down regulated 13 (20.6%) 21 (17.1%) 34 (18.3%) No change 36 (57.1%) 81 (65.9%) 117 (62.9%) Up regulated 14 (22.2%) 21 (17.1%) 35 (18.8%) KLF17 Mutation Categories 0.6971 Down regulated 14 (22.2%) 21 (17.1%) 35 (18.8%) No change 38 (60.3%) 80 (65.0%) 118 (63.4%) Up regulated 11 (17.5%) 22 (17.9%) 33 (17.7%) KSR2 Mutation Categories 0.7631 Down regulated 13 (20.6%) 20 (16.3%) 33 (17.7%) No change 40 (63.5%) 82 (66.7%) 122 (65.6%) Up regulated 10 (15.9%) 21 (17.1%) 31 (16.7%) LRP1B Mutation Categories 0.5931 Down regulated 12 (19.0%) 17 (13.8%) 29 (15.6%) No change 45 (71.4%) 96 (78.0%) 141 (75.8%) Up regulated 6 (9.5%) 10 (8.1%) 16 (8.6%) NKAIN3 Mutation Categories 0.2601 Down regulated 14 (22.2%) 17 (13.8%) 31 (16.7%) No change 42 (66.7%) 95 (77.2%) 137 (73.7%) Up regulated 7 (11.1%) 11 (8.9%) 18 (9.7%) ORM1 Mutation Categories 0.5991 Down regulated 13 (20.6%) 18 (14.6%) 31 (16.7%) No change 44 (69.8%) 93 (75.6%) 137 (73.7%) Up regulated 6 (9.5%) 12 (9.8%) 18 (9.7%) ORM2 Mutation Categories 0.6871 Attorney Docket No.07039-2153WO1 / 2022-168 Down regulated 13 (20.6%) 19 (15.4%) 32 (17.2%) No change 44 (69.8%) 92 (74.8%) 136 (73.1%) Up regulated 6 (9.5%) 12 (9.8%) 18 (9.7%) PKHD1L1 Mutation Categories 0.3221 Down regulated 16 (25.4%) 20 (16.3%) 36 (19.4%) No change 40 (63.5%) 86 (69.9%) 126 (67.7%) Up regulated 7 (11.1%) 17 (13.8%) 24 (12.9%) RELN Mutation Categories 0.8541 Down regulated 10 (15.9%) 18 (14.6%) 28 (15.1%) No change 44 (69.8%) 90 (73.2%) 134 (72.0%) Up regulated 9 (14.3%) 15 (12.2%) 24 (12.9%) SAGE1 Mutation Categories 0.5741 Down regulated 13 (20.6%) 20 (16.3%) 33 (17.7%) No change 39 (61.9%) 85 (69.1%) 124 (66.7%) Up regulated 11 (17.5%) 18 (14.6%) 29 (15.6%) SOAT2 Mutation Categories 0.8331 Down regulated 13 (20.6%) 21 (17.1%) 34 (18.3%) No change 39 (61.9%) 80 (65.0%) 119 (64.0%) Up regulated 11 (17.5%) 22 (17.9%) 33 (17.7%) TMEM150B Mutation Categories 0.6631 Down regulated 11 (17.5%) 23 (18.7%) 34 (18.3%) No change 40 (63.5%) 83 (67.5%) 123 (66.1%) Up regulated 12 (19.0%) 17 (13.8%) 29 (15.6%) TTC16 Mutation Categories 0.8101 Down regulated 13 (20.6%) 21 (17.1%) 34 (18.3%) No change 39 (61.9%) 81 (65.9%) 120 (64.5%) Up regulated 11 (17.5%) 21 (17.1%) 32 (17.2%) UNC13C Mutation Categories 0.8331 Down regulated 13 (20.6%) 21 (17.1%) 34 (18.3%) No change 39 (61.9%) 80 (65.0%) 119 (64.0%) Up regulated 11 (17.5%) 22 (17.9%) 33 (17.7%) 1. Fisher’s Exact Test for Count Data Attorney Docket No.07039-2153WO1 / 2022-168 Genes Associated with Metastasis Logistic LASSO regression was used to identify genes associated with metastasis. Cross-validation was used to choose the optimal λ in the LASSO regression and after λ was fixed the genes were chosen from the model fit. Further, due to the cross-validation variations, 100 times cross-validation was used, and every time the genes that were selected were stored in a matrix. Among the 100 times selections, if the genes have been chosen 50 times or above, then the genes were considered predictive of the metastasis. There were 14 genes were chosen 50 times or more – CDC6, CYP2U1, FN1, MGAM (these 4 genes up- regulated were associated with met status); KIT, CYP2E1, CYP4F3, CALCOCO1, AOX1, EVPL, FASN, PLA2R1, CASP14, and ZNF750 (these 10 genes down-regulated were associated with met status), Therefore, the 14 genes (4 up-regulated and 10 down-regulated) were chosen to generate the risk score for metastasis. Table 9 summarizes the generating risk score comparison by the Met vs. NoMet groups. Using this risk score to predict metastasis, the AUC (area under ROC curve) was 82.0% (95% CI: 75.9% to 88.2%) (Figure 7A). Using 4 as the optimal cut-off to predict metastasis – i.e., patients who had this risk score 4 or above were considered as having metastasis, patients who had this risk score 3 or below were considered as not having metastasis. The sensitivity, specificity and overall accuracy for this cut-off was 65.1%, 80.5% and 75.3%. Table 9. Risk score comparison between met and non-met groups. PMet PNoMet Total (N=63) (N=123) (N=186) p value Risk score for Metastasis < 0.0011 Mean (SD) 4.9 (2.8) 1.8 (2.0) 2.9 (2.7) Median 5.0 1.0 2.0 Q1, Q3 2.5, 7.0 0.0, 3.0 1.0, 4.0 Range 0.0 - 13.0 0.0 - 8.0 0.0 - 13.0 Attorney Docket No.07039-2153WO1 / 2022-168 Risk score for Metastasis < 0.0012 0 1 (1.6%) 40 (32.5%) 41 (22.0%) 1 6 (9.5%) 30 (24.4%) 36 (19.4%) 2 9 (14.3%) 14 (11.4%) 23 (12.4%) 3 6 (9.5%) 15 (12.2%) 21 (11.3%) 4 7 (11.1%) 13 (10.6%) 20 (10.8%) 5 5 (7.9%) 4 (3.3%) 9 (4.8%) 6 10 (15.9%) 2 (1.6%) 12 (6.5%) 7 8 (12.7%) 1 (0.8%) 9 (4.8%) 8 7 (11.1%) 4 (3.3%) 11 (5.9%) 9 2 (3.2%) 0 (0.0%) 2 (1.1%) 12 1 (1.6%) 0 (0.0%) 1 (0.5%) 13 1 (1.6%) 0 (0.0%) 1 (0.5%) Risk score for predicting Metastasis (>= 4) < 0.0012 Met 41 (65.1%) 24 (19.5%) 65 (34.9%) NoMet 22 (34.9%) 99 (80.5%) 121 (65.1%) Risk score for Overall Survival < 0.0011 Mean (SD) 2.1 (1.6) 1.2 (1.5) 1.5 (1.6) Median 2.0 1.0 1.0 Q1, Q3 1.0, 3.0 0.0, 2.0 0.0, 3.0 Range 0.0 - 6.0 0.0 - 6.0 0.0 - 6.0 Risk score for Overall Survival 0.0072 0 14 (22.2%) 53 (43.1%) 67 (36.0%) Attorney Docket No.07039-2153WO1 / 2022-168 1 10 (15.9%) 33 (26.8%) 43 (23.1%) 2 14 (22.2%) 13 (10.6%) 27 (14.5%) 3 12 (19.0%) 10 (8.1%) 22 (11.8%) 4 8 (12.7%) 9 (7.3%) 17 (9.1%) 5 4 (6.3%) 4 (3.3%) 8 (4.3%) 6 1 (1.6%) 1 (0.8%) 2 (1.1%) Risk score for Event-Free Survival < 0.0011 Mean (SD) 2.8 (2.2) 1.2 (1.8) 1.7 (2.1) Median 2.0 0.0 1.0 Q1, Q3 1.0, 5.0 0.0, 2.0 0.0, 3.0 Range 0.0 - 8.0 0.0 - 8.0 0.0 - 8.0 Risk score for Event-Free Survival < 0.0012 0 12 (19.0%) 68 (55.3%) 80 (43.0%) 1 12 (19.0%) 19 (15.4%) 31 (16.7%) 2 9 (14.3%) 10 (8.1%) 19 (10.2%) 3 3 (4.8%) 11 (8.9%) 14 (7.5%) 4 10 (15.9%) 5 (4.1%) 15 (8.1%) 5 8 (12.7%) 7 (5.7%) 15 (8.1%) 6 7 (11.1%) 1 (0.8%) 8 (4.3%) 7 1 (1.6%) 1 (0.8%) 2 (1.1%) 8 1 (1.6%) 1 (0.8%) 2 (1.1%) 1. Linear Model ANOVA 2. Pearson’s Chi-squared test Attorney Docket No.07039-2153WO1 / 2022-168 Genes Associated with Local Recurrence or Metastasis A similar method was used to choose the genes that can predict local recurrence or metastasis – among the 186 samples, there 70 samples which had local recurrence or metastasis (63 of them had metastasis and 7 of them didn’t have metastasis but only local recurrence). Therefore, the genes that were selected here were similar to those that were predictive of metastasis. There was one more gene (TRPM1), which down-regulation was associated with local recurrence or metastasis. Other four genes (KRT28, TCHH, MUC5B and FAM178B) that were selected based on the models but were not significantly associated with local recurrence or metastasis. Therefore, the total 15 genes – 14 genes that were predictive of metastasis plus TRPM1 were used to generate the risk score for predicting local recurrence and metastasis. Table 10 summarizes the generating risk score comparison by the local recurrence/metastasis vs no local recurrence & no metastasis. Using this risk score to predict local recurrence/metastasis, the AUC (area under ROC curve) was 77.3% (95% CI: 70.5% to 84.1%) (Figure 7). Using 4 as the optimal cut-off to predict local recurrence/metastasis – i.e., patients who had this risk score 4 or above were considered as having local recurrence/metastasis, patients who had this risk score 3 or below were considered as not having local recurrence/metastasis. The sensitivity, specificity and overall accuracy for this cut-off was 61.4%, 76.7% and 71.0%. Table 10. Risk score comparison between local recurrence/met and non-local recurrence/met groups No (N=116) Yes (N=70) Total (N=186) p value Risk score for Local recurrence/Metastasis < 0.0011 Mean (SD) 2.0 (2.2) 4.8 (3.0) 3.1 (2.9) Median 1.0 4.5 3.0 Q1, Q3 0.0, 3.0 2.0, 7.0 1.0, 5.0 Attorney Docket No.07039-2153WO1 / 2022-168 Range 0.0 - 9.0 0.0 - 13.0 0.0 - 13.0 Risk score for Local recurrence/Metastasis < 0.0012 0 37 (31.9%) 3 (4.3%) 40 (21.5%) 1 26 (22.4%) 9 (12.9%) 35 (18.8%) 2 10 (8.6%) 7 (10.0%) 17 (9.1%) 3 16 (13.8%) 8 (11.4%) 24 (12.9%) 4 13 (11.2%) 8 (11.4%) 21 (11.3%) 5 6 (5.2%) 4 (5.7%) 10 (5.4%) 6 2 (1.7%) 9 (12.9%) 11 (5.9%) 7 2 (1.7%) 8 (11.4%) 10 (5.4%) 8 2 (1.7%) 8 (11.4%) 10 (5.4%) 9 2 (1.7%) 3 (4.3%) 5 (2.7%) 10 0 (0.0%) 1 (1.4%) 1 (0.5%) 13 0 (0.0%) 2 (2.9%) 2 (1.1%) Risk score for predicting local recurrence/metastasis (>= 4) < 0.0012 Met 27 (23.3%) 43 (61.4%) 70 (37.6%) NoMet 89 (76.7%) 27 (38.6%) 116 (62.4%) 1. Linear Model ANOVA 2. Pearson’s Chi-squared test Genes Associated with Overall Survival To choose the genes that were potentially associated with overall survival, regularized Cox regression (i.e., glmnet for survival data) was used. Similar modeling strategies were used as for the risk score for met status – (1) 100 cross-validation were used to choose the Attorney Docket No.07039-2153WO1 / 2022-168 genes that were associated with overall survival; (2) among the 100 cross-validation models, the genes that were selected 50 times or more were considered. There are 13 genes were considered – CDCA5, CXCL8, PRC1 and ZNF750 (these 4 genes up-regulated were associated with worse survival), KRT2, ALOX12, ALDH3A2, and DMD (these 4 genes down-regulated were associated with worse survival), NQO1, ACAT2, CSMD2, CMYA5, CXCL10 (these 5 genes were not significantly associated with worse survival, so they were not used in the analysis). The other 8 genes (CDCA5, CXCL8, PRC1, ZNF750, KRT2, ALOX12, ALDH3A2, and DMD) were chosen to generate the risk score for overall survival. The risk scores for overall survival were significantly different between Met and Non-Met groups (p<.001, Table 9). The risk score based on the 8 genes stratified the patients for their overall survival (Figures 10A-10B and Table 11). The median survival time for patients with a risk score less than or equal to 1 was 7.8 years, median survival time for patients with risk score between 2 and 4 was 4.4 years and for patients with risk score 5 and 6 was 1.9 years. With every risk score increase, the risk of death increased by 1.28 (HR: 1.28, 95% CI: 1.13 to 1.46, p<.001) after adjusting for age, immunosuppressant use, and metastasis status. The Harrell’s C- statistic for the risk score to predict OS was 65.6%. A subset of KRT2, ALOX12, ALDH3A2, and DMD (Figure 8A-8D) and a subset of CXCL10, ZNF750, CDCA5, and PRC1 (Figure 9A-9D) were also able to stratify the patients. Table 11. Multivariable COX regression model summary for overall survival.
Figure imgf000156_0001
Attorney Docket No.07039-2153WO1 / 2022-168 Genes Associated with Event-Free Survival To choose the genes that were associated with event-free survival (local recurrence, nodal recurrence, metastasis, and death were all treated as events of interest), regularized Cox regression (i.e., glmnet for survival data) was used. Similar modeling strategies were applied. 8 genes were considered – CDCA5 and CEP55 (these 2 genes up-regulated were associated with worse event-free survival), KRT2, ALOX12, CYP4F3, CALCOCO1, ACSL1, and CASP14 (these 6 genes down-regulated were associated with worse event-free survival). These 8 genes were chosen to generate the risk score for event-free survival. The risk scores for event-free survival were significantly different between Met and Non-Met groups (p<.001, Table 9). The risk score based on the 8 genes stratified the patients very well for their event- free survival (Figures 13A-13B and Table 12). The median event-free survival time for patients with risk score 0 was 7.8 years, median event-free survival time for patients with risk score between 2 and 5 was 2.1 years and for patients with risk score between 6 and 8 was 0.2 years. With every risk score increase, the risk of death increased by 1.11 (HR: 1.11, 95% CI: 1.00 to 1.24, p=0.046) after adjusting for age, immunosuppressant use, and metastasis status. The Harrell’s C-statistic for the risk score to predict OS was 66.6%. A subset of KRT2, ALOX12, CYP4F3, CALCOCO1, ACSL1, and CSP14 (Figure 11A-11F) and a subset of CEP55 and CDCA5 (Figure 12A-12B) were also able to stratify the patients. Table 12. Multivariable Cox regression model summary for event-free survival.
Figure imgf000157_0001
Attorney Docket No.07039-2153WO1 / 2022-168 Together these results demonstrate that the molecular signature of a cSCC can be used to predict the patient outcome and can be used to select a treatment based on the predicted outcome(s). In some cases, an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of an CYP2U1 polypeptide (or mRNA encoding an CYP2U1 polypeptide), an altered level of an FN1 polypeptide (or mRNA encoding an FN1 polypeptide), an altered level of a MGAM polypeptide (or mRNA encoding a MGAM polypeptide), an altered level of a KIT polypeptide (or mRNA encoding a KIT polypeptide), an altered level of a CYP2E1 polypeptide (or mRNA encoding a CYP2E1 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a AOX1 polypeptide (or mRNA encoding a AOX1 polypeptide), an altered level of a EVPL polypeptide (or mRNA encoding a EVPL polypeptide), an altered level of a FASN polypeptide (or mRNA encoding a FASN polypeptide), an altered level of a PLA2R1 polypeptide (or mRNA encoding a PLA2R1 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), and/or an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide), in a cancer cells of a mammal (e.g., a human) having a cSCC can be used to identify that cSCC as being likely to metastasize (e.g., likely to metastasize to one or more lymph nodes). For example, an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of an CYP2U1 polypeptide (or mRNA encoding an CYP2U1 polypeptide), an altered level of an FN1 polypeptide (or mRNA encoding an FN1 polypeptide), an altered level of a MGAM polypeptide (or mRNA encoding a MGAM polypeptide), an altered level of a KIT polypeptide (or mRNA encoding a KIT polypeptide), an altered level of a CYP2E1 polypeptide (or mRNA encoding a CYP2E1 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a AOX1 polypeptide (or mRNA encoding a AOX1 polypeptide), an altered level of a EVPL polypeptide (or mRNA encoding a EVPL polypeptide), an altered level of a FASN polypeptide (or mRNA encoding a FASN polypeptide), an altered level of a PLA2R1 polypeptide (or mRNA encoding a PLA2R1 Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide), and/or an altered level of a TRPM1 polypeptide (or mRNA encoding a TRPM1 polypeptide), in a cancer cells of a mammal (e.g., a human) having a cSCC can be used to identify that cSCC as being likely to recur locally and to metastasize (e.g., likely to recur in the same location as the original cSCC location and to metastasize to one or more lymph nodes). In some cases, an altered level of a CXCL8 polypeptide (or mRNA encoding a CXCL8 polypeptide), an altered level of an ZNF750 polypeptide (or mRNA encoding an ZNF750 polypeptide), an altered level of an CDCA5 polypeptide (or mRNA encoding an CDCA5 polypeptide), an altered level of a PRC1 polypeptide (or mRNA encoding a PRC1 polypeptide), an altered level of a KRT2 polypeptide (or mRNA encoding a KRT2 polypeptide), an altered level of a ALOX12 polypeptide (or mRNA encoding a ALOX12 polypeptide), an altered level of a ALOX12 polypeptide (or mRNA encoding a ALOX12 polypeptide), and/or an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), in a cancer cells of a mammal (e.g., a human) having a cSCC can be used to identify that mammal as being likely to experience improved survival (e.g., overall survival). For example, an altered level of a CEP55 polypeptide (or mRNA encoding a CEP55 polypeptide), an altered level of an CDCA5 polypeptide (or mRNA encoding an CDCA5 polypeptide), an altered level of an KRT2 polypeptide (or mRNA encoding an KRT2 polypeptide), an altered level of a ALOX12 polypeptide (or mRNA encoding a ALOX12 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a ACSL1 polypeptide (or mRNA encoding a ACSL1 polypeptide), and/or an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), in a cancer cells of a mammal (e.g., a human) having a cSCC can be used to identify that mammal as being likely to experience improved survival (e.g., an event- free survival). Attorney Docket No.07039-2153WO1 / 2022-168 Example 4: cSCC RNA analysis This analysis looked at the differential expression levels of genes to determine a molecular signature between metastatic and non-metastatic samples, with a total of 128 samples from 125 subjects (3 subjects provided 2 samples each). These samples represent a subset of samples analyzed in Example 3. The results in this Example re-present and expand on at least some of the results provided in other Examples. Figure 14A shows the differential gene expression of the 128 samples studied. The genes included are predictive of outcome including metastasis and survival. Differences were seen between metastatic and non-metastatic tumors across these genes of interest. Patient Population Table 13 shows the patients’ demographics and clinical characteristics of the metastatic (PMet) group compared to non-metastatic (PNoMet) group. There was no significant difference in terms of sex and immunosuppressant use between the two groups. Table 14 shows the tumor characteristic by metastatic (Met) group compared to non- metastatic (No Met) group. There was no significant difference in terms of age at biopsy and tumor stage between the two groups. Table 13. Demographics PMet (N=43) PnoMet (N=82) Total (N=125) p value Sex 0888
Figure imgf000160_0001
Table 14. Tumor characteristics Pmet (N=44) PnoMet (N=84) Total (N=128) p value A 2
Figure imgf000160_0002
Attorney Docket No.07039-2153WO1 / 2022-168 T2b 14 (31.8%) 27 (32.1%) 41 (32.0%) T3 4 (9.1%) 1 (1.2%) 5 (3.9%) 1. Pearson’s Chi-squared test
Figure imgf000161_0001
Gene summary statistics Table 15 shows the categorical data for each gene including demographics, clinical characteristics, and gene mutations by metastatic status. Table 15. Gene Mutations Comparison between the met and non-met groups Pmet (N=44) PnoMet (N=84) Total (N=128) p value ABCA12 Mutation Categories < 0.001 1 1 1 1 1 1 5 6 1
Figure imgf000161_0002
Attorney Docket No.07039-2153WO1 / 2022-168 Up regulated 3 (6.8%) 12 (14.3%) 15 (11.7%) CYP4F22 Mutation Categories < 0.001 Down regulated 31 (70.5%) 15 (17.9%) 46 (35.9%) 1 1 1 1 3 1 1 1 1 1 1 1 1
Figure imgf000162_0001
Attorney Docket No.07039-2153WO1 / 2022-168 PLA2G4E Mutation Categories < 0.001 Down regulated 21 (47.7%) 8 (9.5%) 29 (22.7%) No change 22 (50.0%) 70 (83.3%) 92 (71.9%) 1 1 1 9 1 1 1 0 1 1 1 2 1 2
Figure imgf000163_0001
Attorney Docket No.07039-2153WO1 / 2022-168 Down regulated 19 (43.2%) 13 (15.5%) 32 (25.0%) No change 23 (52.3%) 58 (69.0%) 81 (63.3%) Up regulated 2 (4.5%) 13 (15.5%) 15 (11.7%) 2 8 8 6 6 3 2 4 1 5 5 6 6 3
Figure imgf000164_0001
Attorney Docket No.07039-2153WO1 / 2022-168 No change 29 (65.9%) 53 (63.1%) 82 (64.1%) Up regulated 6 (13.6%) 17 (20.2%) 23 (18.0%) SVEP1 Mutation Categories 0.100 1 1 0 5 6 5 9 2 5 3 6 8 2
Figure imgf000165_0001
Attorney Docket No.07039-2153WO1 / 2022-168 Up regulated 14 (31.8%) 15 (17.9%) 29 (22.7%) CXCL10 Mutation Categories 0.501 Down regulated 6 (13.6%) 13 (15.5%) 19 (14.8%) 9 1 5 9 9 7 2 1 8 8 6 7 4
Figure imgf000166_0001
Attorney Docket No.07039-2153WO1 / 2022-168 AURKA Mutation Categories 0.563 Down regulated 2 (4.5%) 7 (8.3%) 9 (7.0%) No change 35 (79.5%) 68 (81.0%) 103 (80.5%) 8 0 2 7 3 9 1 9 0 8 2 3 6 6
Figure imgf000167_0001
Attorney Docket No.07039-2153WO1 / 2022-168 Down regulated 2 (4.5%) 7 (8.3%) 9 (7.0%) No change 30 (68.2%) 63 (75.0%) 93 (72.7%) Up regulated 12 (27.3%) 14 (16.7%) 26 (20.3%) 5 4 4 1 2 4 0 4 9 5 7 5 7 6
Figure imgf000168_0001
Attorney Docket No.07039-2153WO1 / 2022-168 No change 34 (77.3%) 65 (77.4%) 99 (77.3%) Up regulated 9 (20.5%) 13 (15.5%) 22 (17.2%) TTK Mutation Categories 0.277 3 9 8 1 5 1 1 5 8 3 1 8 4
Figure imgf000169_0001
Attorney Docket No.07039-2153WO1 / 2022-168 Up regulated 2 (4.5%) 14 (16.7%) 16 (12.5%) CYP2C9 Mutation Categories 0.704 Down regulated 10 (22.7%) 14 (16.7%) 24 (18.8%) 5 1 2 2 0 3 4 3 8 7 0 5 1
Figure imgf000170_0001
Attorney Docket No.07039-2153WO1 / 2022-168 ACTA1 Mutation Categories 0.088 Down regulated 4 (9.1%) 5 (6.0%) 9 (7.0%) No change 31 (70.5%) 72 (85.7%) 103 (80.5%) 2 0 3 8 7 3 5 5 0 1 2 4 9 0
Figure imgf000171_0001
Attorney Docket No.07039-2153WO1 / 2022-168 Down regulated 15 (34.1%) 15 (17.9%) 30 (23.4%) No change 28 (63.6%) 55 (65.5%) 83 (64.8%) Up regulated 1 (2.3%) 14 (16.7%) 15 (11.7%) 7 9 3 5 2 2 5 5 7 2 1 8 0 6
Figure imgf000172_0001
Attorney Docket No.07039-2153WO1 / 2022-168 No change 25 (56.8%) 58 (69.0%) 83 (64.8%) Up regulated 9 (20.5%) 11 (13.1%) 20 (15.6%) DLGAP3 Mutation Categories 0.550 4 5 7 7 8 4 4 0 9 5 8 7 4
Figure imgf000173_0001
Attorney Docket No.07039-2153WO1 / 2022-168 Up regulated 8 (18.2%) 11 (13.1%) 19 (14.8%) TMEM150B Mutation Categories 0.755 Down regulated 7 (15.9%) 16 (19.0%) 23 (18.0%) 4 4
Figure imgf000174_0001
Genes Associated with Metastasis Logistic LASSO regression was used to identify genes associated with metastasis. Cross-validation was used to choose the optimal λ in the LASSO regression and after λ was fixed the genes were chosen from the model fit. Further, due to the cross-validation variations, 100 times cross-validation was used, and every time the genes that were selected were stored in a matrix. Among the 100 times selections, if the genes have been chosen 50 times or above, then the genes were considered predictive of the metastasis. There were 17 genes were chosen 50 times or above – FN1, MGAM, CYP2U1 and CDC6 (these 4 genes up-regulated were associated with metastasis), AOX1, EVPL, TRPM1, DMD, PLA2R1, CASP14, CYP4F22, CERS3 (these 8 genes down-regulated were associated with metastasis), FCGBP, TCHH, TPX2, PLK1, and IFNE (there 5 genes were not associated with metastasis in any direction). Therefore, the 12 genes (4 up-regulated and 8 down-regulated) were chosen to generate the risk score for metastasis. Table 16 summarized the generating risk score comparison by the two groups. Using this risk score to predict metastasis, the AUC (area under ROC curve) is 88.9% (95% CI: 82.8% to 94.9%) (Figure 14B). Three was used as the optimal cut-off to predict metastasis – i.e., patients who had this risk score 3 or above were considered as having metastasis, patients who had this risk score 2 or below were considered as not having metastasis. The sensitivity, specificity and overall accuracy for this cut-off was 84.1%, 77.4%, and 79.7%. Table 16. Risk score comparison between met and non-met groups PMet PNoMet Total p
Figure imgf000174_0002
Attorney Docket No.07039-2153WO1 / 2022-168 (N=44) (N=84) (N=128) value Risk score for Metastasis < 0.001 Mean (SD) 5.2 (2.5) 1.4 (1.7) 2.7 (2.7) 1 1 1
Figure imgf000175_0001
Genes Associated with Overall Survival Regularized Cox regression (i.e., glmnet for survival data) was used to identify genes associated with overall survival. A similar modeling strategy was used as described above to identify genes associated with metastatic status. First a 100 cross-validation was done to choose the genes associated with overall survival. Among the 100 cross-validation models, genes that were selected 50 times or more were considered. There are 12 genes were considered – CDCA5, NQO1, ZNF750, CDC6 (these 4 genes up-regulated were associated with worse survival), ALDH3A2, DMD, ALDH1A1, ALOX12, TSGA10 (these 5 genes down-regulated were associated with worse survival), CXCL10, ACAT2, and FAM178B (these 3 genes were not significantly associated with worse survival, so they were not chosen). The other 9 genes were chosen to generate the risk score for overall survival. The risk scores for overall survival were significantly different between metastatic and non- metastatic sample groups (p<.001, Table 17). Attorney Docket No.07039-2153WO1 / 2022-168 The risk score based on the 10 genes stratified the patients very well for their overall survival (Figures 17A-17B and Table 17). The median survival time for patients with risk score less than or equal to 1 was 10.4 years, median survival time for patients with risk score between 2 and 4 was 4.0 years, and median survival time for patients with risk score between 5 and 8 was 1.1 years. With every risk score increase, the risk of death increased by 1.21 (HR: 1.21, 95% CI: 1.04 to 1.41, p=0.012) after adjusting for age, immunosuppressant use, and metastasis status. The Harrell’s C-statistic for the risk score to predict OS is 69.5%. A subset of ALDH3A2, DMD, ALDH1A1, ALOX12, and TSGA10 (Figure 15A-15E) and a subset of CDCA5, NQO1, ZNF750, and CDC6 (Figure 16A-16D) were also able to stratify the patients. Table 17. Multivariable Cox regression model summary for overall survival.
Figure imgf000176_0001
Together these results demonstrate that the molecular signature of a cSCC can be used to predict the patient outcome and can be used to select a treatment based on the predicted outcome(s). For example, an altered level of a FN1 polypeptide (or mRNA encoding a FN1 polypeptide), an altered level of an MGAM polypeptide (or mRNA encoding an MGAM polypeptide), an altered level of an CYP2U1 polypeptide (or mRNA encoding an CYP2U1 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide), an altered level of a EVPL polypeptide (or mRNA encoding a EVPL polypeptide), an altered level of a TRPM1 polypeptide (or mRNA encoding a TRPM1 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a CYP4F22 polypeptide (or mRNA encoding a CYP4F22 polypeptide), and/or an altered level of a CERS3 polypeptide (or mRNA encoding a CERS3 polypeptide), in a cancer cells of a mammal (e.g., a human) having a cSCC can be used to identify that cSCC as being likely to metastasize (e.g., likely to metastasize to one or more lymph nodes). In another example, an altered level of a NQO1 polypeptide (or mRNA encoding a NQO1 polypeptide), an altered level of an ZNF750 polypeptide (or mRNA encoding an ZNF750 polypeptide), an altered level of an CDC6 polypeptide (or mRNA encoding an CDC6 polypeptide), an altered level of a CDCA5 polypeptide (or mRNA encoding a CDCA5 polypeptide), an altered level of a ALDH3A2 polypeptide (or mRNA encoding a ALDH3A2 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a ALDH1A1 polypeptide (or mRNA encoding a ALDH1A1 polypeptide), an altered level of a ALOX12 polypeptide (or mRNA encoding a ALOX12 polypeptide), and/or an altered level of a TSGA10 polypeptide (or mRNA encoding a TSGA10 polypeptide), in a cancer cells of a mammal (e.g., a human) having a cSCC can be used to identify that mammal as being likely to experience improved survival (e.g., overall survival). Example 5: Predicting Survival of a cSCC Patient A tissue sample containing one or more cSCC cells is obtained from a human having cSCC. The obtained sample is examined for the presence or absence of an altered level of a BIRC5 polypeptide (or mRNA encoding a BIRC5 polypeptide), an altered level of a MELK polypeptide (or mRNA encoding a MELK polypeptide), an altered level of an IFNE polypeptide (or mRNA encoding an IFNE polypeptide), an altered level of a HMGCS1 polypeptide (or mRNA encoding a HMGCS1 polypeptide), an altered level of an ANK2 polypeptide (or mRNA encoding an ANK2 polypeptide), an altered level of a LAMA2 Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide (or mRNA encoding a LAMA2 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a FAM13C polypeptide (or mRNA encoding a FAM13C polypeptide), an altered level of a COL25A1 polypeptide (or mRNA encoding a COL25A1 polypeptide), an altered level of a TG polypeptide (or mRNA encoding a TG polypeptide), an altered level of a FAT4 polypeptide (or mRNA encoding a FAT4 polypeptide), an altered level of an ACSL1 polypeptide (or mRNA encoding an ACSL1 polypeptide), an altered level of an ALDH1A1 polypeptide (or mRNA encoding an ALDH1A1 polypeptide), an altered level of an ALDH3A2 polypeptide (or mRNA encoding an ALDH3A2 polypeptide), an altered level of an ALOX12 polypeptide (or mRNA encoding an ALOX12 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of a CDCA5 polypeptide (or mRNA encoding a CDCA5 polypeptide), an altered level of a CEP55 polypeptide (or mRNA encoding a CEP55 polypeptide), an altered level of a CXCL8 polypeptide (or mRNA encoding a CXCL8 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a KRT2 polypeptide (or mRNA encoding a KRT2 polypeptide), an altered level of a NQO1 polypeptide (or mRNA encoding a NQO1 polypeptide), an altered level of a PRC1 polypeptide (or mRNA encoding a PRC1 polypeptide), an altered level of a TSGA10 polypeptide (or mRNA encoding a TSGA10 polypeptide), and an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide). If the presence of one or more of an altered level of a BIRC5 polypeptide (or mRNA encoding a BIRC5 polypeptide), an altered level of a MELK polypeptide (or mRNA encoding a MELK polypeptide), an altered level of an IFNE polypeptide (or mRNA encoding an IFNE polypeptide), an altered level of a HMGCS1 polypeptide (or mRNA encoding a HMGCS1 polypeptide), an altered level of an ANK2 polypeptide (or mRNA encoding an ANK2 polypeptide), an altered level of a LAMA2 polypeptide (or mRNA encoding a LAMA2 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a Attorney Docket No.07039-2153WO1 / 2022-168 CYP2U1 polypeptide), an altered level of a FAM13C polypeptide (or mRNA encoding a FAM13C polypeptide), an altered level of a COL25A1 polypeptide (or mRNA encoding a COL25A1 polypeptide), an altered level of a TG polypeptide (or mRNA encoding a TG polypeptide), an altered level of a FAT4 polypeptide (or mRNA encoding a FAT4 polypeptide), an altered level of an ACSL1 polypeptide (or mRNA encoding an ACSL1 polypeptide), an altered level of an ALDH1A1 polypeptide (or mRNA encoding an ALDH1A1 polypeptide), an altered level of an ALDH3A2 polypeptide (or mRNA encoding an ALDH3A2 polypeptide), an altered level of an ALOX12 polypeptide (or mRNA encoding an ALOX12 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of a CDCA5 polypeptide (or mRNA encoding a CDCA5 polypeptide), an altered level of a CEP55 polypeptide (or mRNA encoding a CEP55 polypeptide), an altered level of a CXCL8 polypeptide (or mRNA encoding a CXCL8 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a KRT2 polypeptide (or mRNA encoding a KRT2 polypeptide), an altered level of a NQO1 polypeptide (or mRNA encoding a NQO1 polypeptide), an altered level of a PRC1 polypeptide (or mRNA encoding a PRC1 polypeptide), an altered level of a TSGA10 polypeptide (or mRNA encoding a TSGA10 polypeptide), and an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide) is detected in the sample, then the human is classified as being likely to experience prolonged survival from cSCC (e.g., prolonged survival from the time of cSCC diagnosis). If the sample lacks an altered level of a BIRC5 polypeptide (or mRNA encoding a BIRC5 polypeptide), an altered level of a MELK polypeptide (or mRNA encoding a MELK polypeptide), an altered level of an IFNE polypeptide (or mRNA encoding an IFNE polypeptide), an altered level of a HMGCS1 polypeptide (or mRNA encoding a HMGCS1 polypeptide), an altered level of an ANK2 polypeptide (or mRNA encoding an ANK2 polypeptide), an altered level of a LAMA2 polypeptide (or mRNA encoding a LAMA2 Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a FAM13C polypeptide (or mRNA encoding a FAM13C polypeptide), an altered level of a COL25A1 polypeptide (or mRNA encoding a COL25A1 polypeptide), an altered level of a TG polypeptide (or mRNA encoding a TG polypeptide), an altered level of a FAT4 polypeptide (or mRNA encoding a FAT4 polypeptide), an altered level of an ACSL1 polypeptide (or mRNA encoding an ACSL1 polypeptide), an altered level of an ALDH1A1 polypeptide (or mRNA encoding an ALDH1A1 polypeptide), an altered level of an ALDH3A2 polypeptide (or mRNA encoding an ALDH3A2 polypeptide), an altered level of an ALOX12 polypeptide (or mRNA encoding an ALOX12 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of a CDCA5 polypeptide (or mRNA encoding a CDCA5 polypeptide), an altered level of a CEP55 polypeptide (or mRNA encoding a CEP55 polypeptide), an altered level of a CXCL8 polypeptide (or mRNA encoding a CXCL8 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a KRT2 polypeptide (or mRNA encoding a KRT2 polypeptide), an altered level of a NQO1 polypeptide (or mRNA encoding a NQO1 polypeptide), an altered level of a PRC1 polypeptide (or mRNA encoding a PRC1 polypeptide), an altered level of a TSGA10 polypeptide (or mRNA encoding a TSGA10 polypeptide), and an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide), then the human is classified as not being likely to experience prolonged survival from cSCC (e.g., not being likely to survive for about 2 or more years from the time of cSCC diagnosis). Example 6: Predicting cSCC Metastasis A tissue sample containing one or more cSCC cells is obtained from a human having cSCC. The obtained sample is examined for the presence or absence of an altered level of a CSAG1 polypeptide (or mRNA encoding a CSAG1 polypeptide), an altered level of an UBE2C polypeptide (or mRNA encoding an UBE2C polypeptide), an altered level of an Attorney Docket No.07039-2153WO1 / 2022-168 ANKRD1 polypeptide (or mRNA encoding an ANKRD1 polypeptide), an altered level of a CSMD3 polypeptide (or mRNA encoding a CSMD3 polypeptide), an altered level of a TOP2A polypeptide (or mRNA encoding a TOP2A polypeptide), an altered level of a TPX2 polypeptide (or mRNA encoding a TPX2 polypeptide), an altered level of a KSR2 polypeptide (or mRNA encoding a KSR2 polypeptide), an altered level of a CSMD2 polypeptide (or mRNA encoding a CSMD2 polypeptide), an altered level of a MMP20 polypeptide (or mRNA encoding a MMP20 polypeptide), an altered level of a PCSK1 polypeptide (or mRNA encoding a PCSK1 polypeptide), an altered level of a TMEM150B polypeptide (or mRNA encoding a TMEM150B polypeptide), an altered level of an ACSL1 polypeptide (or mRNA encoding an ACSL1 polypeptide), an altered level of a TSGA10 polypeptide (or mRNA encoding a TSGA10 polypeptide), an altered level of a KIT polypeptide (or mRNA encoding a KIT polypeptide), an altered level of a RGL3 polypeptide (or mRNA encoding a RGL3 polypeptide), an altered level of a PLA2G6 polypeptide (or mRNA encoding a PLA2G6 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of a FN1 polypeptide (or mRNA encoding a FN1 polypeptide), an altered level of a MGAM polypeptide (or mRNA encoding a MGAM polypeptide), an altered level of an EVPL polypeptide (or mRNA encoding an EVPL polypeptide), an altered level of an AOX1 polypeptide (or mRNA encoding an AOX1 polypeptide), an altered level of a PLA2R1 polypeptide (or mRNA encoding a PLA2R1 polypeptide), an altered level of a TRPM1 polypeptide (or mRNA encoding a TRPM1 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a CYP4F22 polypeptide (or mRNA encoding a CYP4F22 polypeptide), an altered level of a CERS3 polypeptide (or mRNA encoding a CERS3 polypeptide), an altered level of a KIT polypeptide (or mRNA encoding a KIT polypeptide), an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), Attorney Docket No.07039-2153WO1 / 2022-168 an altered level of a CYP2E1 polypeptide (or mRNA encoding a CYP2E1 polypeptide), and an altered level of a FASN polypeptide (or mRNA encoding a FASN polypeptide). If the presence of one or more of an altered level of a CSAG1 polypeptide (or mRNA encoding a CSAG1 polypeptide), an altered level of an UBE2C polypeptide (or mRNA encoding an UBE2C polypeptide), an altered level of an ANKRD1 polypeptide (or mRNA encoding an ANKRD1 polypeptide), an altered level of a CSMD3 polypeptide (or mRNA encoding a CSMD3 polypeptide), an altered level of a TOP2A polypeptide (or mRNA encoding a TOP2A polypeptide), an altered level of a TPX2 polypeptide (or mRNA encoding a TPX2 polypeptide), an altered level of a KSR2 polypeptide (or mRNA encoding a KSR2 polypeptide), an altered level of a CSMD2 polypeptide (or mRNA encoding a CSMD2 polypeptide), an altered level of a MMP20 polypeptide (or mRNA encoding a MMP20 polypeptide), an altered level of a PCSK1 polypeptide (or mRNA encoding a PCSK1 polypeptide), an altered level of a TMEM150B polypeptide (or mRNA encoding a TMEM150B polypeptide), an altered level of an ACSL1 polypeptide (or mRNA encoding an ACSL1 polypeptide), an altered level of a TSGA10 polypeptide (or mRNA encoding a TSGA10 polypeptide), an altered level of a KIT polypeptide (or mRNA encoding a KIT polypeptide), an altered level of a RGL3 polypeptide (or mRNA encoding a RGL3 polypeptide), an altered level of a PLA2G6 polypeptide (or mRNA encoding a PLA2G6 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of a FN1 polypeptide (or mRNA encoding a FN1 polypeptide), an altered level of a MGAM polypeptide (or mRNA encoding a MGAM polypeptide), an altered level of an EVPL polypeptide (or mRNA encoding an EVPL polypeptide), an altered level of an AOX1 polypeptide (or mRNA encoding an AOX1 polypeptide), an altered level of a PLA2R1 polypeptide (or mRNA encoding a PLA2R1 polypeptide), an altered level of a TRPM1 polypeptide (or mRNA encoding a TRPM1 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a CYP4F22 polypeptide (or mRNA encoding a CYP4F22 polypeptide), an altered level of a CERS3 polypeptide (or mRNA encoding a CERS3 polypeptide), an altered level of a KIT Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide (or mRNA encoding a KIT polypeptide), an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a CYP2E1 polypeptide (or mRNA encoding a CYP2E1 polypeptide), and an altered level of a FASN polypeptide (or mRNA encoding a FASN polypeptide) is detected in the sample, then the cSCC is classified as being likely to metastasize (e.g., likely to metastasize to one or more lymph nodes). If the sample lacks an altered level of a CSAG1 polypeptide (or mRNA encoding a CSAG1 polypeptide), an altered level of an UBE2C polypeptide (or mRNA encoding an UBE2C polypeptide), an altered level of an ANKRD1 polypeptide (or mRNA encoding an ANKRD1 polypeptide), an altered level of a CSMD3 polypeptide (or mRNA encoding a CSMD3 polypeptide), an altered level of a TOP2A polypeptide (or mRNA encoding a TOP2A polypeptide), an altered level of a TPX2 polypeptide (or mRNA encoding a TPX2 polypeptide), an altered level of a KSR2 polypeptide (or mRNA encoding a KSR2 polypeptide), an altered level of a CSMD2 polypeptide (or mRNA encoding a CSMD2 polypeptide), an altered level of a MMP20 polypeptide (or mRNA encoding a MMP20 polypeptide), an altered level of a PCSK1 polypeptide (or mRNA encoding a PCSK1 polypeptide), an altered level of a TMEM150B polypeptide (or mRNA encoding a TMEM150B polypeptide), an altered level of an ACSL1 polypeptide (or mRNA encoding an ACSL1 polypeptide), an altered level of a TSGA10 polypeptide (or mRNA encoding a TSGA10 polypeptide), an altered level of a KIT polypeptide (or mRNA encoding a KIT polypeptide), an altered level of a RGL3 polypeptide (or mRNA encoding a RGL3 polypeptide), an altered level of a PLA2G6 polypeptide (or mRNA encoding a PLA2G6 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of a FN1 polypeptide (or mRNA encoding a FN1 polypeptide), an altered level of a MGAM polypeptide (or mRNA encoding a MGAM polypeptide), an altered level of an EVPL polypeptide (or mRNA encoding an EVPL polypeptide), an altered Attorney Docket No.07039-2153WO1 / 2022-168 level of an AOX1 polypeptide (or mRNA encoding an AOX1 polypeptide), an altered level of a PLA2R1 polypeptide (or mRNA encoding a PLA2R1 polypeptide), an altered level of a TRPM1 polypeptide (or mRNA encoding a TRPM1 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a CYP4F22 polypeptide (or mRNA encoding a CYP4F22 polypeptide), an altered level of a CERS3 polypeptide (or mRNA encoding a CERS3 polypeptide), an altered level of a KIT polypeptide (or mRNA encoding a KIT polypeptide), an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a CYP2E1 polypeptide (or mRNA encoding a CYP2E1 polypeptide), and an altered level of a FASN polypeptide (or mRNA encoding a FASN polypeptide), then the cSCC is classified as not being likely to metastasize. Example 7: Treating cSCC A tissue sample containing one or more cSCC cells is obtained from a human having cSCC. The obtained sample is examined for the presence or absence of an altered level of a BIRC5 polypeptide (or mRNA encoding a BIRC5 polypeptide), an altered level of a MELK polypeptide (or mRNA encoding a MELK polypeptide), an altered level of an IFNE polypeptide (or mRNA encoding an IFNE polypeptide), an altered level of a HMGCS1 polypeptide (or mRNA encoding a HMGCS1 polypeptide), an altered level of an ANK2 polypeptide (or mRNA encoding an ANK2 polypeptide), an altered level of a LAMA2 polypeptide (or mRNA encoding a LAMA2 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a FAM13C polypeptide (or mRNA encoding a FAM13C polypeptide), an altered level of a COL25A1 polypeptide (or mRNA encoding a COL25A1 polypeptide), an altered level of a TG polypeptide (or mRNA encoding a TG polypeptide), an altered level of a FAT4 polypeptide (or mRNA encoding a FAT4 polypeptide), an altered level of an ACSL1 polypeptide (or mRNA encoding an ACSL1 polypeptide), an altered level of an ALDH1A1 polypeptide (or mRNA encoding an ALDH1A1 polypeptide), an altered level of an ALDH3A2 polypeptide Attorney Docket No.07039-2153WO1 / 2022-168 (or mRNA encoding an ALDH3A2 polypeptide), an altered level of an ALOX12 polypeptide (or mRNA encoding an ALOX12 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of a CDCA5 polypeptide (or mRNA encoding a CDCA5 polypeptide), an altered level of a CEP55 polypeptide (or mRNA encoding a CEP55 polypeptide), an altered level of a CXCL8 polypeptide (or mRNA encoding a CXCL8 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a KRT2 polypeptide (or mRNA encoding a KRT2 polypeptide), an altered level of a NQO1 polypeptide (or mRNA encoding a NQO1 polypeptide), an altered level of a PRC1 polypeptide (or mRNA encoding a PRC1 polypeptide), an altered level of a TSGA10 polypeptide (or mRNA encoding a TSGA10 polypeptide), and an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide). If the presence of one or more of an altered level of a BIRC5 polypeptide (or mRNA encoding a BIRC5 polypeptide), an altered level of a MELK polypeptide (or mRNA encoding a MELK polypeptide), an altered level of an IFNE polypeptide (or mRNA encoding an IFNE polypeptide), an altered level of a HMGCS1 polypeptide (or mRNA encoding a HMGCS1 polypeptide), an altered level of an ANK2 polypeptide (or mRNA encoding an ANK2 polypeptide), an altered level of a LAMA2 polypeptide (or mRNA encoding a LAMA2 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a FAM13C polypeptide (or mRNA encoding a FAM13C polypeptide), an altered level of a COL25A1 polypeptide (or mRNA encoding a COL25A1 polypeptide), an altered level of a TG polypeptide (or mRNA encoding a TG polypeptide), an altered level of a FAT4 polypeptide (or mRNA encoding a FAT4 polypeptide), an altered level of an ACSL1 polypeptide (or mRNA encoding an ACSL1 polypeptide), an altered level of an ALDH1A1 polypeptide (or mRNA encoding an ALDH1A1 polypeptide), an altered level of an ALDH3A2 polypeptide (or mRNA encoding an ALDH3A2 polypeptide), an altered level of an ALOX12 polypeptide (or mRNA encoding Attorney Docket No.07039-2153WO1 / 2022-168 an ALOX12 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of a CDCA5 polypeptide (or mRNA encoding a CDCA5 polypeptide), an altered level of a CEP55 polypeptide (or mRNA encoding a CEP55 polypeptide), an altered level of a CXCL8 polypeptide (or mRNA encoding a CXCL8 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a KRT2 polypeptide (or mRNA encoding a KRT2 polypeptide), an altered level of a NQO1 polypeptide (or mRNA encoding a NQO1 polypeptide), an altered level of a PRC1 polypeptide (or mRNA encoding a PRC1 polypeptide), an altered level of a TSGA10 polypeptide (or mRNA encoding a TSGA10 polypeptide), and an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide) is detected in the sample, then the human having a cSCC is identified as being likely to experience prolonged survival from cSCC (e.g., likely to survive for about 2 or more years from the time of cSCC diagnosis), and the human is subjected to surgery to remove the cSCC without any adjuvant therapy. The surgery can reduce number of cancer cells within the human while sparing the human from unnecessary risks and/or complications associated with SNL biopsies. Example 8: Treating cSCC A tissue sample containing one or more cSCC cells is obtained from a human having cSCC. The obtained sample is examined for the presence or absence of an altered level of a BIRC5 polypeptide (or mRNA encoding a BIRC5 polypeptide), an altered level of a MELK polypeptide (or mRNA encoding a MELK polypeptide), an altered level of an IFNE polypeptide (or mRNA encoding an IFNE polypeptide), an altered level of a HMGCS1 polypeptide (or mRNA encoding a HMGCS1 polypeptide), an altered level of an ANK2 polypeptide (or mRNA encoding an ANK2 polypeptide), an altered level of a LAMA2 polypeptide (or mRNA encoding a LAMA2 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a FAM13C Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide (or mRNA encoding a FAM13C polypeptide), an altered level of a COL25A1 polypeptide (or mRNA encoding a COL25A1 polypeptide), an altered level of a TG polypeptide (or mRNA encoding a TG polypeptide), an altered level of a FAT4 polypeptide (or mRNA encoding a FAT4 polypeptide), an altered level of an ACSL1 polypeptide (or mRNA encoding an ACSL1 polypeptide), an altered level of an ALDH1A1 polypeptide (or mRNA encoding an ALDH1A1 polypeptide), an altered level of an ALDH3A2 polypeptide (or mRNA encoding an ALDH3A2 polypeptide), an altered level of an ALOX12 polypeptide (or mRNA encoding an ALOX12 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of a CDCA5 polypeptide (or mRNA encoding a CDCA5 polypeptide), an altered level of a CEP55 polypeptide (or mRNA encoding a CEP55 polypeptide), an altered level of a CXCL8 polypeptide (or mRNA encoding a CXCL8 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a KRT2 polypeptide (or mRNA encoding a KRT2 polypeptide), an altered level of a NQO1 polypeptide (or mRNA encoding a NQO1 polypeptide), an altered level of a PRC1 polypeptide (or mRNA encoding a PRC1 polypeptide), an altered level of a TSGA10 polypeptide (or mRNA encoding a TSGA10 polypeptide), and an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide). If the sample lacks an increased level of an altered level of a BIRC5 polypeptide (or mRNA encoding a BIRC5 polypeptide), an altered level of a MELK polypeptide (or mRNA encoding a MELK polypeptide), an altered level of an IFNE polypeptide (or mRNA encoding an IFNE polypeptide), an altered level of a HMGCS1 polypeptide (or mRNA encoding a HMGCS1 polypeptide), an altered level of an ANK2 polypeptide (or mRNA encoding an ANK2 polypeptide), an altered level of a LAMA2 polypeptide (or mRNA encoding a LAMA2 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a FAM13C polypeptide (or mRNA encoding a FAM13C polypeptide), an altered level of a COL25A1 polypeptide (or mRNA encoding a Attorney Docket No.07039-2153WO1 / 2022-168 COL25A1 polypeptide), an altered level of a TG polypeptide (or mRNA encoding a TG polypeptide), an altered level of a FAT4 polypeptide (or mRNA encoding a FAT4 polypeptide), an altered level of an ACSL1 polypeptide (or mRNA encoding an ACSL1 polypeptide), an altered level of an ALDH1A1 polypeptide (or mRNA encoding an ALDH1A1 polypeptide), an altered level of an ALDH3A2 polypeptide (or mRNA encoding an ALDH3A2 polypeptide), an altered level of an ALOX12 polypeptide (or mRNA encoding an ALOX12 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of a CDCA5 polypeptide (or mRNA encoding a CDCA5 polypeptide), an altered level of a CEP55 polypeptide (or mRNA encoding a CEP55 polypeptide), an altered level of a CXCL8 polypeptide (or mRNA encoding a CXCL8 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a KRT2 polypeptide (or mRNA encoding a KRT2 polypeptide), an altered level of a NQO1 polypeptide (or mRNA encoding a NQO1 polypeptide), an altered level of a PRC1 polypeptide (or mRNA encoding a PRC1 polypeptide), an altered level of a TSGA10 polypeptide (or mRNA encoding a TSGA10 polypeptide), and an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide), then the human is identified as not being likely to experience prolonged survival from cSCC (e.g., not being likely to survive for about 2 or more years from the time of cSCC diagnosis), and the human is subjected to surgery to remove the cSCC and is administered one or more adjuvant therapies. The surgery in combination with the one or more adjuvant therapies can reduce number of cancer cells within the human while improving the overall survival (e.g., overall survival) of the human. Example 9: Treating cSCC A tissue sample containing one or more cSCC cells is obtained from a human having cSCC. The obtained sample is examined for the presence or absence of an altered level of a Attorney Docket No.07039-2153WO1 / 2022-168 CSAG1 polypeptide (or mRNA encoding a CSAG1 polypeptide), an altered level of an UBE2C polypeptide (or mRNA encoding an UBE2C polypeptide), an altered level of an ANKRD1 polypeptide (or mRNA encoding an ANKRD1 polypeptide), an altered level of a CSMD3 polypeptide (or mRNA encoding a CSMD3 polypeptide), an altered level of a TOP2A polypeptide (or mRNA encoding a TOP2A polypeptide), an altered level of a TPX2 polypeptide (or mRNA encoding a TPX2 polypeptide), an altered level of a KSR2 polypeptide (or mRNA encoding a KSR2 polypeptide), an altered level of a CSMD2 polypeptide (or mRNA encoding a CSMD2 polypeptide), an altered level of a MMP20 polypeptide (or mRNA encoding a MMP20 polypeptide), an altered level of a PCSK1 polypeptide (or mRNA encoding a PCSK1 polypeptide), an altered level of a TMEM150B polypeptide (or mRNA encoding a TMEM150B polypeptide), an altered level of an ACSL1 polypeptide (or mRNA encoding an ACSL1 polypeptide), an altered level of a TSGA10 polypeptide (or mRNA encoding a TSGA10 polypeptide), an altered level of a KIT polypeptide (or mRNA encoding a KIT polypeptide), an altered level of a RGL3 polypeptide (or mRNA encoding a RGL3 polypeptide), an altered level of a PLA2G6 polypeptide (or mRNA encoding a PLA2G6 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of a FN1 polypeptide (or mRNA encoding a FN1 polypeptide), an altered level of a MGAM polypeptide (or mRNA encoding a MGAM polypeptide), an altered level of an EVPL polypeptide (or mRNA encoding an EVPL polypeptide), an altered level of an AOX1 polypeptide (or mRNA encoding an AOX1 polypeptide), an altered level of a PLA2R1 polypeptide (or mRNA encoding a PLA2R1 polypeptide), an altered level of a TRPM1 polypeptide (or mRNA encoding a TRPM1 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a CYP4F22 polypeptide (or mRNA encoding a CYP4F22 polypeptide), an altered level of a CERS3 polypeptide (or mRNA encoding a CERS3 polypeptide), an altered level of a KIT polypeptide (or mRNA encoding a KIT polypeptide), an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an Attorney Docket No.07039-2153WO1 / 2022-168 altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a CYP2E1 polypeptide (or mRNA encoding a CYP2E1 polypeptide), and an altered level of a FASN polypeptide (or mRNA encoding a FASN polypeptide). If the presence of one or more of an altered level of a CSAG1 polypeptide (or mRNA encoding a CSAG1 polypeptide), an altered level of an UBE2C polypeptide (or mRNA encoding an UBE2C polypeptide), an altered level of an ANKRD1 polypeptide (or mRNA encoding an ANKRD1 polypeptide), an altered level of a CSMD3 polypeptide (or mRNA encoding a CSMD3 polypeptide), an altered level of a TOP2A polypeptide (or mRNA encoding a TOP2A polypeptide), an altered level of a TPX2 polypeptide (or mRNA encoding a TPX2 polypeptide), an altered level of a KSR2 polypeptide (or mRNA encoding a KSR2 polypeptide), an altered level of a CSMD2 polypeptide (or mRNA encoding a CSMD2 polypeptide), an altered level of a MMP20 polypeptide (or mRNA encoding a MMP20 polypeptide), an altered level of a PCSK1 polypeptide (or mRNA encoding a PCSK1 polypeptide), an altered level of a TMEM150B polypeptide (or mRNA encoding a TMEM150B polypeptide), an altered level of an ACSL1 polypeptide (or mRNA encoding an ACSL1 polypeptide), an altered level of a TSGA10 polypeptide (or mRNA encoding a TSGA10 polypeptide), an altered level of a KIT polypeptide (or mRNA encoding a KIT polypeptide), an altered level of a RGL3 polypeptide (or mRNA encoding a RGL3 polypeptide), an altered level of a PLA2G6 polypeptide (or mRNA encoding a PLA2G6 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of a FN1 polypeptide (or mRNA encoding a FN1 polypeptide), an altered level of a MGAM polypeptide (or mRNA encoding a MGAM polypeptide), an altered level of an EVPL polypeptide (or mRNA encoding an EVPL polypeptide), an altered level of an AOX1 polypeptide (or mRNA encoding an AOX1 polypeptide), an altered level of a PLA2R1 polypeptide (or mRNA encoding a PLA2R1 polypeptide), an altered level of a TRPM1 polypeptide (or mRNA encoding a TRPM1 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a CYP4F22 polypeptide (or mRNA encoding a CYP4F22 polypeptide), an altered level of a CERS3 Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide (or mRNA encoding a CERS3 polypeptide), an altered level of a KIT polypeptide (or mRNA encoding a KIT polypeptide), an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a CYP2E1 polypeptide (or mRNA encoding a CYP2E1 polypeptide), and an altered level of a FASN polypeptide (or mRNA encoding a FASN polypeptide) is detected in the sample, then the cSCC is identified as being likely to metastasize (e.g., likely to metastasize to one or more lymph nodes), and the human is subjected to surgery to remove the cSCC and is administered one or more adjuvant therapies. The surgery in combination with the one or more adjuvant therapies can reduce number of cancer cells within the human while minimizing the risk of metastasis. Example 10: Treating cSCC A tissue sample containing one or more cSCC cells is obtained from a human having cSCC. The obtained sample is examined for the presence or absence of an altered level of a CSAG1 polypeptide (or mRNA encoding a CSAG1 polypeptide), an altered level of an UBE2C polypeptide (or mRNA encoding an UBE2C polypeptide), an altered level of an ANKRD1 polypeptide (or mRNA encoding an ANKRD1 polypeptide), an altered level of a CSMD3 polypeptide (or mRNA encoding a CSMD3 polypeptide), an altered level of a TOP2A polypeptide (or mRNA encoding a TOP2A polypeptide), an altered level of a TPX2 polypeptide (or mRNA encoding a TPX2 polypeptide), an altered level of a KSR2 polypeptide (or mRNA encoding a KSR2 polypeptide), an altered level of a CSMD2 polypeptide (or mRNA encoding a CSMD2 polypeptide), an altered level of a MMP20 polypeptide (or mRNA encoding a MMP20 polypeptide), an altered level of a PCSK1 polypeptide (or mRNA encoding a PCSK1 polypeptide), an altered level of a TMEM150B polypeptide (or mRNA encoding a TMEM150B polypeptide), an altered level of an ACSL1 polypeptide (or mRNA encoding an ACSL1 polypeptide), an altered level of a TSGA10 polypeptide (or mRNA encoding a TSGA10 polypeptide), an altered level of a KIT polypeptide (or mRNA encoding a KIT polypeptide), an altered level of a RGL3 polypeptide Attorney Docket No.07039-2153WO1 / 2022-168 (or mRNA encoding a RGL3 polypeptide), an altered level of a PLA2G6 polypeptide (or mRNA encoding a PLA2G6 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of a FN1 polypeptide (or mRNA encoding a FN1 polypeptide), an altered level of a MGAM polypeptide (or mRNA encoding a MGAM polypeptide), an altered level of an EVPL polypeptide (or mRNA encoding an EVPL polypeptide), an altered level of an AOX1 polypeptide (or mRNA encoding an AOX1 polypeptide), an altered level of a PLA2R1 polypeptide (or mRNA encoding a PLA2R1 polypeptide), an altered level of a TRPM1 polypeptide (or mRNA encoding a TRPM1 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a CYP4F22 polypeptide (or mRNA encoding a CYP4F22 polypeptide), an altered level of a CERS3 polypeptide (or mRNA encoding a CERS3 polypeptide), an altered level of a KIT polypeptide (or mRNA encoding a KIT polypeptide), an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a CYP2E1 polypeptide (or mRNA encoding a CYP2E1 polypeptide), and an altered level of a FASN polypeptide (or mRNA encoding a FASN polypeptide). If the sample lacks an increased level of an altered level of a CSAG1 polypeptide (or mRNA encoding a CSAG1 polypeptide), an altered level of an UBE2C polypeptide (or mRNA encoding an UBE2C polypeptide), an altered level of an ANKRD1 polypeptide (or mRNA encoding an ANKRD1 polypeptide), an altered level of a CSMD3 polypeptide (or mRNA encoding a CSMD3 polypeptide), an altered level of a TOP2A polypeptide (or mRNA encoding a TOP2A polypeptide), an altered level of a TPX2 polypeptide (or mRNA encoding a TPX2 polypeptide), an altered level of a KSR2 polypeptide (or mRNA encoding a KSR2 polypeptide), an altered level of a CSMD2 polypeptide (or mRNA encoding a CSMD2 polypeptide), an altered level of a MMP20 polypeptide (or mRNA encoding a MMP20 polypeptide), an altered level of a PCSK1 polypeptide (or mRNA encoding a PCSK1 polypeptide), an altered level of a TMEM150B polypeptide (or mRNA encoding a Attorney Docket No.07039-2153WO1 / 2022-168 TMEM150B polypeptide), an altered level of an ACSL1 polypeptide (or mRNA encoding an ACSL1 polypeptide), an altered level of a TSGA10 polypeptide (or mRNA encoding a TSGA10 polypeptide), an altered level of a KIT polypeptide (or mRNA encoding a KIT polypeptide), an altered level of a RGL3 polypeptide (or mRNA encoding a RGL3 polypeptide), an altered level of a PLA2G6 polypeptide (or mRNA encoding a PLA2G6 polypeptide), an altered level of a CYP2U1 polypeptide (or mRNA encoding a CYP2U1 polypeptide), an altered level of a CASP14 polypeptide (or mRNA encoding a CASP14 polypeptide), an altered level of a CDC6 polypeptide (or mRNA encoding a CDC6 polypeptide), an altered level of a FN1 polypeptide (or mRNA encoding a FN1 polypeptide), an altered level of a MGAM polypeptide (or mRNA encoding a MGAM polypeptide), an altered level of an EVPL polypeptide (or mRNA encoding an EVPL polypeptide), an altered level of an AOX1 polypeptide (or mRNA encoding an AOX1 polypeptide), an altered level of a PLA2R1 polypeptide (or mRNA encoding a PLA2R1 polypeptide), an altered level of a TRPM1 polypeptide (or mRNA encoding a TRPM1 polypeptide), an altered level of a DMD polypeptide (or mRNA encoding a DMD polypeptide), an altered level of a CYP4F22 polypeptide (or mRNA encoding a CYP4F22 polypeptide), an altered level of a CERS3 polypeptide (or mRNA encoding a CERS3 polypeptide), an altered level of a KIT polypeptide (or mRNA encoding a KIT polypeptide), an altered level of a ZNF750 polypeptide (or mRNA encoding a ZNF750 polypeptide), an altered level of a CYP4F3 polypeptide (or mRNA encoding a CYP4F3 polypeptide), an altered level of a CALCOCO1 polypeptide (or mRNA encoding a CALCOCO1 polypeptide), an altered level of a CYP2E1 polypeptide (or mRNA encoding a CYP2E1 polypeptide), and an altered level of a FASN polypeptide (or mRNA encoding a FASN polypeptide), then the cSCC is identified as not being likely to metastasize (e.g., not being likely to metastasize to one or more lymph nodes), and the human is subjected to surgery to remove the cSCC without any adjuvant therapy. The surgery can reduce number of cancer cells within the human while sparing the human from unnecessary risks and/or complications associated with SNL biopsies. Attorney Docket No.07039-2153WO1 / 2022-168 OTHER EMBODIMENTS It is to be understood that while the invention has been described in conjunction with the detailed description thereof, the foregoing description is intended to illustrate and not limit the scope of the invention, which is defined by the scope of the appended claims. Other aspects, advantages, and modifications are within the scope of the following claims.

Claims

Attorney Docket No.07039-2153WO1 / 2022-168 WHAT IS CLAIMED IS: 1. A method for assessing a mammal having a cutaneous squamous cell carcinoma (cSCC), wherein said method comprises: (a) determining if a sample from said mammal contains the presence or absence of at least one of (1) an altered level of a baculoviral IAP repeat-containing protein 5 (BIRC5) polypeptide or mRNA encoding a BIRC5 polypeptide, (2) an altered level of a maternal embryonic leucine zipper kinase (MELK) polypeptide or mRNA encoding a MELK polypeptide, (3) an altered level of an interferon epsilon (IFNE) polypeptide or mRNA encoding an IFNE polypeptide, (4) an altered level of a hydroxymethylglutaryl-CoA synthase, cytoplasmic (HMGCS1) polypeptide or mRNA encoding a HMGCS1 polypeptide, (5) an altered level of an ankyrin-2 (ANK2) polypeptide or mRNA encoding an ANK2 polypeptide, (6) an altered level of a laminin subunit alpha-2 (LAMA2) polypeptide or mRNA encoding a LAMA2 polypeptide, (7) an altered level of a cytochrome P4502U1 (CYP2U1) polypeptide or mRNA encoding a CYP2U1 polypeptide, (8) an altered level of a family with sequence similarity 13 member C (FAM13C) polypeptide or mRNA encoding a FAM13C polypeptide, (9) an altered level of a collagen alpha-1 (XXV) chain (COL25A1) polypeptide or mRNA encoding a COL25A1 polypeptide, (10) an altered level of a thyroglobulin (TG) polypeptide or mRNA encoding a TG polypeptide, and (11) an altered level of a protocadherin Fat 4 (FAT4) polypeptide or mRNA encoding a FAT4 polypeptide; (b) classifying said mammal as being likely to experience a higher survival rate if said presence is determined; and (c) classifying said mammal as not being likely to experience a higher survival rate if said absence of each of (1)-(11) is determined. 2. The method of claim 1, wherein said mammal is a human. 3. The method of any one of claims 1-2, wherein the presence or absence of said altered level of said BIRC5 polypeptide is determined. Attorney Docket No.07039-2153WO1 / 2022-168 4. The method of any one of claims 1-2, wherein the presence or absence of said altered level of said MELK polypeptide is determined. 5. The method of any one of claims 1-2, wherein the presence or absence of said altered level of said IFNE polypeptide is determined. 6. The method of any one of claims 1-2, wherein the presence or absence of said altered level of said HMGCS1 polypeptide is determined. 7. The method of any one of claims 1-2, wherein the presence or absence of said altered level of said ANK2 polypeptide is determined. 8. The method of any one of claims 1-2, wherein the presence or absence of said altered level of said LAMA2 polypeptide is determined. 9. The method of any one of claims 1-2, wherein the presence or absence of said altered level of said CYP2U1 polypeptide is determined. 10. The method of any one of claims 1-2, wherein the presence or absence of said altered level of said FAM13C polypeptide is determined. 11. The method of any one of claims 1-2, wherein the presence or absence of said altered level of said COL25A1 polypeptide is determined. 12. The method of any one of claims 1-2, wherein the presence or absence of said altered level of said TG polypeptide is determined. 13. The method of any one of claims 1-2, wherein the presence or absence of said altered level of said FAT4 polypeptide is determined. Attorney Docket No.07039-2153WO1 / 2022-168 14. The method of any one of claims 1-13, wherein said sample is a tissue sample comprising a cSCC cell. 15. A method for assessing a mammal having a cSCC, wherein said method comprises: (a) determining if a sample from said mammal contains the presence or absence of at least one of (1) an altered level of a chondrosarcoma-associated gene 1 (CSAG1) polypeptide or mRNA encoding a CSAG1 polypeptide, (2) an altered level of an ubiquitin-conjugating enzyme E2 C (UBE2C) polypeptide or mRNA encoding an UBE2C polypeptide, (3) an altered level of an ankyrin repeat domain-containing protein 1 (ANKRD1) polypeptide or mRNA encoding an ANKRD1 polypeptide, (4) an altered level of a CUB and sushi domain- containing protein 3 (CSMD3) polypeptide or mRNA encoding a CSMD3 polypeptide, (5) an altered level of a topoisomerase 2-alpha (TOP2A) polypeptide or mRNA encoding a TOP2A polypeptide, (6) an altered level of a targeting protein for Xklp2 (TPX2) polypeptide or mRNA encoding a TPX2 polypeptide, (7) an altered level of a kinase suppressor of Ras 2 (KSR2) polypeptide or mRNA encoding a KSR2 polypeptide, (8) an altered level of a CUB and sushi domain-containing protein 2 (CSMD2) polypeptide or mRNA encoding a CSMD2 polypeptide, (9) an altered level of a matrix metalloproteinase-20 preproprotein (MMP20) polypeptide or mRNA encoding a MMP20 polypeptide, (10) an altered level of a neuroendocrine convertase 1 (PCSK1) polypeptide or mRNA encoding a PCSK1 polypeptide, (11) an altered level of a transmembrane protein 150B (TMEM150B) polypeptide or mRNA encoding a TMEM150B polypeptide, (12) an altered level of an acyl- CoA synthetase long chain family member 1 (ACSL1) polypeptide or mRNA encoding an ACSL1 polypeptide, (13) an altered level of a testis-specific gene 10 (TSGA10) polypeptide or mRNA encoding a TSGA10 polypeptide, (14) an altered level of a proto-oncogene c-Kit (KIT) polypeptide or mRNA encoding a KIT polypeptide, (15) an altered level of a ral guanine nucleotide dissociation stimulator-like 3 (RGL3) polypeptide or mRNA encoding a RGL3 polypeptide, and (16) an altered level of a 85/88 kDa calcium-independent phospholipase A2 (PLA2G6) polypeptide or mRNA encoding a PLA2G6 polypeptide; (b) classifying said cSCC as being likely to metastasize if said presence is determined; and Attorney Docket No.07039-2153WO1 / 2022-168 (c) classifying said cSCC as not being likely to metastasize if said absence of each of (1)-(16) is determined. 16. The method of claim 15, wherein said mammal is a human. 17. The method of any one of claims 15-16, wherein the presence or absence of said altered level of said CSAG1 polypeptide is determined. 18. The method of any one of claims 15-16, wherein the presence or absence of said altered level of said UBE2C polypeptide is determined. 19. The method of any one of claims 15-16, wherein the presence or absence of said altered level of said ANKRD1 polypeptide is determined. 20. The method of any one of claims 15-16, wherein the presence or absence of said altered level of said CSMD3 polypeptide is determined. 21. The method of any one of claims 15-16, wherein the presence or absence of said altered level of said TOP2A polypeptide is determined. 22. The method of any one of claims 15-16, wherein the presence or absence of said altered level of said TPX2 polypeptide is determined. 23. The method of any one of claims 15-16, wherein the presence or absence of said altered level of said KSR2 polypeptide is determined. 24. The method of any one of claims 15-16, wherein the presence or absence of said altered level of said CSMD2 polypeptide is determined. Attorney Docket No.07039-2153WO1 / 2022-168 25. The method of any one of claims 15-16, wherein the presence or absence of said altered level of said MMP20 polypeptide is determined. 26. The method of any one of claims 15-16, wherein the presence or absence of said altered level of said PCSK1 polypeptide is determined. 27. The method of any one of claims 15-16, wherein the presence or absence of said altered level of said TMEM150B polypeptide is determined. 28. The method of any one of claims 15-16, wherein the presence or absence of said altered level of said ACSL1 polypeptide is determined. 29. The method of any one of claims 15-16, wherein the presence or absence of said altered level of said TSGA10 polypeptide is determined. 30. The method of any one of claims 15-16, wherein the presence or absence of said altered level of said KIT polypeptide is determined. 31. The method of any one of claims 15-16, wherein the presence or absence of said altered level of said RGL3 polypeptide is determined. 32. The method of any one of claims 15-16, wherein the presence or absence of said altered level of said PLA2G6 polypeptide is determined. 33. The method of any one of claims 15-32, wherein said sample is a tissue sample comprising a cSCC cell. 34. A method for selecting a treatment for a mammal having a cSCC, wherein said method comprises: (a) determining that a sample from said mammal contains: Attorney Docket No.07039-2153WO1 / 2022-168 the absence of (a-1) an altered level of a BIRC5 polypeptide or mRNA encoding a BIRC5 polypeptide, (a-2) an altered level of a MELK polypeptide or mRNA encoding a MELK polypeptide, (a-3) an altered level of an IFNE polypeptide or mRNA encoding an IFNE polypeptide, (a-4) an altered level of a HMGCS1 polypeptide or mRNA encoding a HMGCS1 polypeptide, (a-5) an altered level of an ANK2 polypeptide or mRNA encoding an ANK2 polypeptide, (a-6) an altered level of a LAMA2 polypeptide or mRNA encoding a LAMA2 polypeptide, (a-7) an altered level of a CYP2U1 polypeptide or mRNA encoding a CYP2U1 polypeptide, (a-8) an altered level of a FAM13C polypeptide or mRNA encoding a FAM13C polypeptide, (a-9) an altered level of a COL25A1 polypeptide or mRNA encoding a COL25A1 polypeptide, (a-10) an altered level of a TG polypeptide or mRNA encoding a TG polypeptide, and (a-11) an altered level of a FAT4 polypeptide or mRNA encoding a FAT4 polypeptide; or the presence of at least one of (a-12) an altered level of a CSAG1 polypeptide or mRNA encoding a CSAG1 polypeptide, (a-13) an altered level of an UBE2C polypeptide or mRNA encoding an UBE2C polypeptide, (a-14) an altered level of an ANKRD1 polypeptide or mRNA encoding an ANKRD1 polypeptide, (a-15) an altered level of a CSMD3 polypeptide or mRNA encoding a CSMD3 polypeptide, (a-16) an altered level of a TOP2A polypeptide or mRNA encoding a TOP2A polypeptide, (a-17) an altered level of a TPX2 polypeptide or mRNA encoding a TPX2 polypeptide, (a-18) an altered level of a KSR2 polypeptide or mRNA encoding a KSR2 polypeptide, (a-19) an altered level of a CSMD2 polypeptide or mRNA encoding a CSMD2 polypeptide, (a-20) an altered level of a MMP20 polypeptide or mRNA encoding a MMP20 polypeptide, (a-21) an altered level of a PCSK1 polypeptide or mRNA encoding a PCSK1 polypeptide, (a-22) an altered level of a TMEM150B polypeptide or mRNA encoding a TMEM150B polypeptide, (a-23) an altered level of an ACSL1 polypeptide or mRNA encoding an ACSL1 polypeptide, (a-24) an altered level of a TSGA10 polypeptide or mRNA encoding a TSGA10 polypeptide, (a-25) an altered level of a KIT polypeptide or mRNA encoding a KIT polypeptide, (a-26) an altered level of a RGL3 polypeptide or mRNA encoding a RGL3 polypeptide, and (a-27) an altered level of a PLA2G6 polypeptide or mRNA encoding a PLA2G6 polypeptide; and Attorney Docket No.07039-2153WO1 / 2022-168 (b) selecting said mammal for surgery to remove said cSCC and to receive an adjuvant therapy. 35. A method for selecting a treatment for a mammal having a cSCC, wherein said method comprises: (a) determining that a sample from said mammal contains: the presence of at least one of (a-1) an altered level of a BIRC5 polypeptide or mRNA encoding a BIRC5 polypeptide, (a-2) an altered level of a MELK polypeptide or mRNA encoding a MELK polypeptide, (a-3) an altered level of an IFNE polypeptide or mRNA encoding an IFNE polypeptide, (a-4) an altered level of a HMGCS1 polypeptide or mRNA encoding a HMGCS1 polypeptide, (a-5) an altered level of an ANK2 polypeptide or mRNA encoding an ANK2 polypeptide, (a-6) an altered level of a LAMA2 polypeptide or mRNA encoding a LAMA2 polypeptide, (a-7) an altered level of a CYP2U1 polypeptide or mRNA encoding a CYP2U1 polypeptide, (a-8) an altered level of a FAM13C polypeptide or mRNA encoding a FAM13C polypeptide, (a-9) an altered level of a COL25A1 polypeptide or mRNA encoding a COL25A1 polypeptide, (a-10) an altered level of a TG polypeptide or mRNA encoding a TG polypeptide, and (a-11) an altered level of a FAT4 polypeptide or mRNA encoding a FAT4 polypeptide; or the absence of (a-12) an altered level of a CSAG1 polypeptide or mRNA encoding a CSAG1 polypeptide, (a-13) an altered level of an UBE2C polypeptide or mRNA encoding an UBE2C polypeptide, (a-14) an altered level of an ANKRD1 polypeptide or mRNA encoding an ANKRD1 polypeptide, (a-15) an altered level of a CSMD3 polypeptide or mRNA encoding a CSMD3 polypeptide, (a-16) an altered level of a TOP2A polypeptide or mRNA encoding a TOP2A polypeptide, (a-17) an altered level of a TPX2 polypeptide or mRNA encoding a TPX2 polypeptide, (a-18) an altered level of a KSR2 polypeptide or mRNA encoding a KSR2 polypeptide, (a-19) an altered level of a CSMD2 polypeptide or mRNA encoding a CSMD2 polypeptide, (a-20) an altered level of a MMP20 polypeptide or mRNA encoding a MMP20 polypeptide, (a-21) an altered level of a PCSK1 polypeptide or mRNA encoding a PCSK1 polypeptide, (a-22) an altered level of a TMEM150B polypeptide or mRNA encoding a TMEM150B polypeptide, (a-23) an altered level of an ACSL1 Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide or mRNA encoding an ACSL1 polypeptide, (a-24) an altered level of a TSGA10 polypeptide or mRNA encoding a TSGA10 polypeptide, (a-25) an altered level of a KIT polypeptide or mRNA encoding a KIT polypeptide, (a-26) an altered level of a RGL3 polypeptide or mRNA encoding a RGL3 polypeptide, and (a-27) an altered level of a PLA2G6 polypeptide or mRNA encoding a PLA2G6 polypeptide; and (b) selecting said mammal for surgery to remove said cSCC in the absence of an adjuvant therapy. 36. The method of any one of claims 34-35, wherein said mammal is a human. 37. The method of any one of claims 34-36, wherein said adjuvant therapy comprises radiation therapy. 38. The method of any one of claims 34-36, wherein said adjuvant therapy comprises administering an anti-cancer drug to said mammal. 39. The method of claim 38, wherein said anti-cancer drug is selected from the group consisting of cemiplimab-rwlc, nivolumab, ipilimumab, pembrolizumab, talimogene laherparepvec, cetuximab, capecitabine, carboplatin, and fluorouracil (5-FU). 40. A method for treating a mammal having a cSCC, wherein said method comprises: (a) determining that a sample from said mammal contains: the absence of (a-1) an altered level of a BIRC5 polypeptide or mRNA encoding a BIRC5 polypeptide, (a-2) an altered level of a MELK polypeptide or mRNA encoding a MELK polypeptide, (a-3) an altered level of an IFNE polypeptide or mRNA encoding an IFNE polypeptide, (a-4) an altered level of a HMGCS1 polypeptide or mRNA encoding a HMGCS1 polypeptide, (a-5) an altered level of an ANK2 polypeptide or mRNA encoding an ANK2 polypeptide, (a-6) an altered level of a LAMA2 polypeptide or mRNA encoding a LAMA2 polypeptide, (a-7) an altered level of a CYP2U1 polypeptide or mRNA encoding a CYP2U1 polypeptide, (a-8) an altered level of a FAM13C polypeptide or mRNA encoding a Attorney Docket No.07039-2153WO1 / 2022-168 FAM13C polypeptide, (a-9) an altered level of a COL25A1 polypeptide or mRNA encoding a COL25A1 polypeptide, (a-10) an altered level of a TG polypeptide or mRNA encoding a TG polypeptide, and (a-11) an altered level of a FAT4 polypeptide or mRNA encoding a FAT4 polypeptide; or the presence of at least one of (a-12) an altered level of a CSAG1 polypeptide or mRNA encoding a CSAG1 polypeptide, (a-13) an altered level of an UBE2C polypeptide or mRNA encoding an UBE2C polypeptide, (a-14) an altered level of an ANKRD1 polypeptide or mRNA encoding an ANKRD1 polypeptide, (a-15) an altered level of a CSMD3 polypeptide or mRNA encoding a CSMD3 polypeptide, (a-16) an altered level of a TOP2A polypeptide or mRNA encoding a TOP2A polypeptide, (a-17) an altered level of a TPX2 polypeptide or mRNA encoding a TPX2 polypeptide, (a-18) an altered level of a KSR2 polypeptide or mRNA encoding a KSR2 polypeptide, (a-19) an altered level of a CSMD2 polypeptide or mRNA encoding a CSMD2 polypeptide, (a-20) an altered level of a MMP20 polypeptide or mRNA encoding a MMP20 polypeptide, (a-21) an altered level of a PCSK1 polypeptide or mRNA encoding a PCSK1 polypeptide, (a-22) an altered level of a TMEM150B polypeptide or mRNA encoding a TMEM150B polypeptide, (a-23) an altered level of an ACSL1 polypeptide or mRNA encoding an ACSL1 polypeptide, (a-24) an altered level of a TSGA10 polypeptide or mRNA encoding a TSGA10 polypeptide, (a-25) an altered level of a KIT polypeptide or mRNA encoding a KIT polypeptide, (a-26) an altered level of a RGL3 polypeptide or mRNA encoding a RGL3 polypeptide, and (a-27) an altered level of a PLA2G6 polypeptide or mRNA encoding a PLA2G6 polypeptide; (b) subjecting said mammal to a surgery to remove said cSCC; and (c) administering an adjuvant therapy to said mammal. 41. A method for treating a cSCC, wherein said method comprises subjecting a mammal identified as having a sample comprising (a) or (b) to a surgery to remove said cSCC and administering an adjuvant therapy to said mammal, wherein said (a) comprises the absence of (a-1) an altered level of a BIRC5 polypeptide or mRNA encoding a BIRC5 polypeptide, (a-2) an altered level of a MELK polypeptide or mRNA encoding a MELK polypeptide, (a-3) an altered level of an IFNE polypeptide or mRNA encoding an IFNE polypeptide, (a-4) an Attorney Docket No.07039-2153WO1 / 2022-168 altered level of a HMGCS1 polypeptide or mRNA encoding a HMGCS1 polypeptide, (a-5) an altered level of an ANK2 polypeptide or mRNA encoding an ANK2 polypeptide, (a-6) an altered level of a LAMA2 polypeptide or mRNA encoding a LAMA2 polypeptide, (a-7) an altered level of a CYP2U1 polypeptide or mRNA encoding a CYP2U1 polypeptide, (a-8) an altered level of a FAM13C polypeptide or mRNA encoding a FAM13C polypeptide, (a-9) an altered level of a COL25A1 polypeptide or mRNA encoding a COL25A1 polypeptide, (a-10) an altered level of a TG polypeptide or mRNA encoding a TG polypeptide, and (a-11) an altered level of a FAT4 polypeptide or mRNA encoding a FAT4 polypeptide, and wherein said (b) comprises the presence of at least one of (b-1) an altered level of a CSAG1 polypeptide or mRNA encoding a CSAG1 polypeptide, (b-2) an altered level of an UBE2C polypeptide or mRNA encoding an UBE2C polypeptide, (b-3) an altered level of an ANKRD1 polypeptide or mRNA encoding an ANKRD1 polypeptide, (b-4) an altered level of a CSMD3 polypeptide or mRNA encoding a CSMD3 polypeptide, (b-5) an altered level of a TOP2A polypeptide or mRNA encoding a TOP2A polypeptide, (b-6) an altered level of a TPX2 polypeptide or mRNA encoding a TPX2 polypeptide, (b-7) an altered level of a KSR2 polypeptide or mRNA encoding a KSR2 polypeptide, (b-8) an altered level of a CSMD2 polypeptide or mRNA encoding a CSMD2 polypeptide, (b-9) an altered level of a MMP20 polypeptide or mRNA encoding a MMP20 polypeptide, (b-10) an altered level of a PCSK1 polypeptide or mRNA encoding a PCSK1 polypeptide, (b-11) an altered level of a TMEM150B polypeptide or mRNA encoding a TMEM150B polypeptide, (b-12) an altered level of an ACSL1 polypeptide or mRNA encoding an ACSL1 polypeptide, (b-13) an altered level of a TSGA10 polypeptide or mRNA encoding a TSGA10 polypeptide, (b-14) an altered level of a KIT polypeptide or mRNA encoding a KIT polypeptide, (b-15) an altered level of a RGL3 polypeptide or mRNA encoding a RGL3 polypeptide, and (b-16) an altered level of a PLA2G6 polypeptide or mRNA encoding a PLA2G6 polypeptide. 42. The method of any one of claims 40-41, wherein said mammal is a human. 43. The method of any one of claims 40-42, wherein said sample is a tissue sample comprising a cSCC cell. Attorney Docket No.07039-2153WO1 / 2022-168 44. The method of any one of claims 40-43, wherein said adjuvant therapy comprises radiation therapy. 45. The method of any one of claims 40-43, wherein said adjuvant therapy comprises administering an anti-cancer drug to said mammal. 46. The method of claim 45, wherein said anti-cancer drug is selected from the group consisting of cemiplimab-rwlc, nivolumab, ipilimumab, pembrolizumab, talimogene laherparepvec, cetuximab, capecitabine, carboplatin, and 5-FU. 47. A method for treating a mammal having a cSCC, wherein said method comprises: (a) determining if a sample from said mammal comprises: the presence of at least one of (a-1) an altered level of a BIRC5 polypeptide or mRNA encoding a BIRC5 polypeptide, (a-2) an altered level of a MELK polypeptide or mRNA encoding a MELK polypeptide, (a-3) an altered level of an IFNE polypeptide or mRNA encoding an IFNE polypeptide, (a-4) an altered level of a HMGCS1 polypeptide or mRNA encoding a HMGCS1 polypeptide, (a-5) an altered level of an ANK2 polypeptide or mRNA encoding an ANK2 polypeptide, (a-6) an altered level of a LAMA2 polypeptide or mRNA encoding a LAMA2 polypeptide, (a-7) an altered level of a CYP2U1 polypeptide or mRNA encoding a CYP2U1 polypeptide, (a-8) an altered level of a FAM13C polypeptide or mRNA encoding a FAM13C polypeptide, (a-9) an altered level of a COL25A1 polypeptide or mRNA encoding a COL25A1 polypeptide, (a-10) an altered level of a TG polypeptide or mRNA encoding a TG polypeptide, and (a-11) an altered level of a FAT4 polypeptide or mRNA encoding a FAT4 polypeptide; or the absence of (a-12) an altered level of a CSAG1 polypeptide or mRNA encoding a CSAG1 polypeptide, (a-13) an altered level of an UBE2C polypeptide or mRNA encoding an UBE2C polypeptide, (a-14) an altered level of an ANKRD1 polypeptide or mRNA encoding an ANKRD1 polypeptide, (a-15) an altered level of a CSMD3 polypeptide or mRNA encoding a CSMD3 polypeptide, (a-16) an altered level of a TOP2A polypeptide or mRNA Attorney Docket No.07039-2153WO1 / 2022-168 encoding a TOP2A polypeptide, (a-17) an altered level of a TPX2 polypeptide or mRNA encoding a TPX2 polypeptide, (a-18) an altered level of a KSR2 polypeptide or mRNA encoding a KSR2 polypeptide, (a-19) an altered level of a CSMD2 polypeptide or mRNA encoding a CSMD2 polypeptide, (a-20) an altered level of a MMP20 polypeptide or mRNA encoding a MMP20 polypeptide, (a-21) an altered level of a PCSK1 polypeptide or mRNA encoding a PCSK1 polypeptide, (a-22) an altered level of a TMEM150B polypeptide or mRNA encoding a TMEM150B polypeptide, (a-23) an altered level of an ACSL1 polypeptide or mRNA encoding an ACSL1 polypeptide, (a-24) an altered level of a TSGA10 polypeptide or mRNA encoding a TSGA10 polypeptide, (a-25) an altered level of a KIT polypeptide or mRNA encoding a KIT polypeptide, (a-26) an altered level of a RGL3 polypeptide or mRNA encoding a RGL3 polypeptide, and (a-27) an altered level of a PLA2G6 polypeptide or mRNA encoding a PLA2G6 polypeptide; and (b) subjecting said mammal to a surgery to remove said cSCC in the absence of an adjuvant therapy. 48. A method for treating cSCC, wherein said method comprises subjecting a mammal identified as comprising a sample comprising (a) or (b) to a surgery to remove said cSCC in the absence of an adjuvant therapy, wherein said (a) comprises the presence of at least one of (a-1) an altered level of a BIRC5 polypeptide or mRNA encoding a BIRC5 polypeptide, (a-2) an altered level of a MELK polypeptide or mRNA encoding a MELK polypeptide, (a-3) an altered level of an IFNE polypeptide or mRNA encoding an IFNE polypeptide, (a-4) an altered level of a HMGCS1 polypeptide or mRNA encoding a HMGCS1 polypeptide, (a-5) an altered level of an ANK2 polypeptide or mRNA encoding an ANK2 polypeptide, (a-6) an altered level of a LAMA2 polypeptide or mRNA encoding a LAMA2 polypeptide, (a-7) an altered level of a CYP2U1 polypeptide or mRNA encoding a CYP2U1 polypeptide, (a-8) an altered level of a FAM13C polypeptide or mRNA encoding a FAM13C polypeptide, (a-9) an altered level of a COL25A1 polypeptide or mRNA encoding a COL25A1 polypeptide, (a-10) an altered level of a TG polypeptide or mRNA encoding a TG polypeptide, and (a-11) an altered level of a FAT4 polypeptide or mRNA encoding a FAT4 polypeptide, and wherein said (b) comprises the absence of (b-1) an altered level of a CSAG1 polypeptide or mRNA Attorney Docket No.07039-2153WO1 / 2022-168 encoding a CSAG1 polypeptide, (b-2) an altered level of an UBE2C polypeptide or mRNA encoding an UBE2C polypeptide, (b-3) an altered level of an ANKRD1 polypeptide or mRNA encoding an ANKRD1 polypeptide, (b-4) an altered level of a CSMD3 polypeptide or mRNA encoding a CSMD3 polypeptide, (b-5) an altered level of a TOP2A polypeptide or mRNA encoding a TOP2A polypeptide, (b-6) an altered level of a TPX2 polypeptide or mRNA encoding a TPX2 polypeptide, (b-7) an altered level of a KSR2 polypeptide or mRNA encoding a KSR2 polypeptide, (b-8) an altered level of a CSMD2 polypeptide or mRNA encoding a CSMD2 polypeptide, (b-9) an altered level of a MMP20 polypeptide or mRNA encoding a MMP20 polypeptide, (b-10) an altered level of a PCSK1 polypeptide or mRNA encoding a PCSK1 polypeptide, (b-11) an altered level of a TMEM150B polypeptide or mRNA encoding a TMEM150B polypeptide, (b-12) an altered level of an ACSL1 polypeptide or mRNA encoding an ACSL1 polypeptide, (b-13) an altered level of a TSGA10 polypeptide or mRNA encoding a TSGA10 polypeptide, (b-14) an altered level of a KIT polypeptide or mRNA encoding a KIT polypeptide, (b-15) an altered level of a RGL3 polypeptide or mRNA encoding a RGL3 polypeptide, and (b-16) an altered level of a PLA2G6 polypeptide or mRNA encoding a PLA2G6 polypeptide. 49. The method of any one of claims 47-48, wherein said mammal is a human. 50. The method of any one of claims 47-49, wherein said sample is a tissue sample comprising a cSCC cell. 51. The method of any one of claims 47-50, wherein said adjuvant therapy comprises radiation therapy. 52. The method of any one of claims 47-50, wherein said adjuvant therapy comprises administering an anti-cancer drug to said mammal. Attorney Docket No.07039-2153WO1 / 2022-168 53. The method of claim 52, wherein said anti-cancer drug is selected from the group consisting of cemiplimab-rwlc, nivolumab, ipilimumab, pembrolizumab, talimogene laherparepvec, cetuximab, capecitabine, carboplatin, and 5-FU. 54. A method for assessing a mammal having a cutaneous squamous cell carcinoma (cSCC), wherein said method comprises: (a) determining if a sample from said mammal contains the presence or absence of at least one of (1) an altered level of an acyl-CoA synthetase long chain family member 1 (ACSL1) polypeptide or mRNA encoding an ACSL1 polypeptide, (2) an altered level of an aldehyde dehydrogenase 1 family member A1 (ALDH1A1) polypeptide or mRNA encoding an ALDH1A1 polypeptide, (3) an altered level of an aldehyde dehydrogenase 3 family member A2 (ALDH3A2) polypeptide or mRNA encoding an ALDH3A2 polypeptide, (4) an altered level of an arachidonate 12-lipoxygenase, 12S type (ALOX12) polypeptide or mRNA encoding an ALOX12 polypeptide, (5) an altered level of a calcium binding and coiled-coil domain 1 (CALCOCO1) polypeptide or mRNA encoding an CALCOCO1 polypeptide, (6) an altered level of a caspase 14 (CASP14) polypeptide or mRNA encoding an CASP14 polypeptide, (7) an altered level of a cell division cycle 6 (CDC6) polypeptide or mRNA encoding an CDC6 polypeptide, (8) an altered level of a cell division cycle-associated 5 (CDCA5) polypeptide or mRNA encoding an CDCA5 polypeptide, (9) an altered level of a centrosomal protein 55 (CEP55) polypeptide or mRNA encoding an CEP55 polypeptide, (10) an altered level of a C-X-C motif chemokine ligand 8 (CXCL8) polypeptide or mRNA encoding an CXCL8 polypeptide, (11) an altered level of a cytochrome P450 family 4 subfamily F member 3 (CYP4F3) polypeptide or mRNA encoding an CYP4F3 polypeptide, (12) an altered level of a dystrophin (DMD) polypeptide or mRNA encoding an DMD polypeptide, (13) an altered level of a keratin 2 (KRT2) polypeptide or mRNA encoding an KRT2 polypeptide, (14) an altered level of a NAD(P)H quinone dehydrogenase 1 (NQO1) polypeptide or mRNA encoding an NQO1 polypeptide, (15) an altered level of a protein regulator of cytokinesis 1 (PRC1) polypeptide or mRNA encoding an PRC1 polypeptide, (16) an altered level of a testis specific 10 (TSGA10) polypeptide or mRNA encoding an Attorney Docket No.07039-2153WO1 / 2022-168 TSGA10 polypeptide, and (17) an altered level of a zinc finger protein 750 (ZNF750) polypeptide or mRNA encoding an ZNF750 polypeptide; (b) classifying said mammal as being likely to experience a higher survival rate if said presence is determined; and (c) classifying said mammal as not being likely to experience a higher survival rate if said absence of each of (1)-(17) is determined. 55. The method of claim 54, wherein said mammal is a human. 56. The method of any one of claims 54-55, wherein the presence or absence of said altered level of said ACSL1 polypeptide is determined. 57. The method of any one of claims 54-55, wherein the presence or absence of said altered level of said ALDH1A1 polypeptide is determined. 58. The method of any one of claims 54-55, wherein the presence or absence of said altered level of said ALDH3A2 polypeptide is determined. 59. The method of any one of claims 54-55, wherein the presence or absence of said altered level of said ALOX12 polypeptide is determined. 60. The method of any one of claims 54-55, wherein the presence or absence of said altered level of said CALCOCO1 polypeptide is determined. 61. The method of any one of claims 54-55, wherein the presence or absence of said altered level of said CASP14 polypeptide is determined. 62. The method of any one of claims 54-55, wherein the presence or absence of said altered level of said CDC6 polypeptide is determined. Attorney Docket No.07039-2153WO1 / 2022-168 63. The method of any one of claims 54-55, wherein the presence or absence of said altered level of said CDCA5 polypeptide is determined. 64. The method of any one of claims 54-55, wherein the presence or absence of said altered level of said CEP55 polypeptide is determined. 65. The method of any one of claims 54-55, wherein the presence or absence of said altered level of said CXCL8 polypeptide is determined. 66. The method of any one of claims 54-55, wherein the presence or absence of said altered level of said CYP4F3 polypeptide is determined. 67. The method of any one of claims 54-55, wherein the presence or absence of said altered level of said DMD polypeptide is determined. 68. The method of any one of claims 54-55, wherein the presence or absence of said altered level of said KRT2 polypeptide is determined. 69. The method of any one of claims 54-55, wherein the presence or absence of said altered level of said NQO1 polypeptide is determined. 70. The method of any one of claims 54-55, wherein the presence or absence of said altered level of said PRC1 polypeptide is determined. 71. The method of any one of claims 54-55, wherein the presence or absence of said altered level of said TSGA10 polypeptide is determined. 72. The method of any one of claims 54-55, wherein the presence or absence of said altered level of said ZNF750 polypeptide is determined. Attorney Docket No.07039-2153WO1 / 2022-168 73. The method of any one of claims 54-72, wherein said sample is a tissue sample comprising a cSCC cell. 74. A method for assessing a mammal having a cSCC, wherein said method comprises: (a) determining if a sample from said mammal contains the presence or absence of at least one of (1) an altered level of an aldehyde oxidase 1 (AOX1) polypeptide or mRNA encoding an AOX1 polypeptide, (2) an altered level of a calcium binding and coiled-coil domain 1 (CALCOCO1) polypeptide or mRNA encoding an CALCOCO1 polypeptide, (3) an altered level of a caspase 14 (CASP14) polypeptide or mRNA encoding an CASP14 polypeptide, (4) an altered level of a cell division cycle 6 (CDC6) polypeptide or mRNA encoding an CDC6 polypeptide, (5) an altered level of a ceramide synthase 3 (CERS3) polypeptide or mRNA encoding an CERS3 polypeptide, (6) an altered level of a cytochrome P450 family 2 subfamily E member 1 (CYP2E1) polypeptide or mRNA encoding an CYP2E1 polypeptide, (7) an altered level of a cytochrome P450 family 2 subfamily U member 1 (CYP2U1) polypeptide or mRNA encoding an CYP2U1 polypeptide, (8) an altered level of a cytochrome P450 family 4 subfamily F member 22 (CYP4F22) polypeptide or mRNA encoding an CYP4F22 polypeptide, (9) an altered level of a cytochrome P450 family 4 subfamily F member 3 (CYP4F3) polypeptide or mRNA encoding an CYP4F3 polypeptide, (10) an altered level of a dystrophin (DMD) polypeptide or mRNA encoding an DMD polypeptide, (11) an altered level of an envoplakin (EVPL) polypeptide or mRNA encoding an EVPL polypeptide, (12) an altered level of a fatty acid synthase (FASN) polypeptide or mRNA encoding an FASN polypeptide, (13) an altered level of a fibronectin 1 (FN1) polypeptide or mRNA encoding an FN1 polypeptide, (14) an altered level of a KIT proto- oncogene (KIT) polypeptide or mRNA encoding an KIT polypeptide, (15) an altered level of a maltase-glucoamylase (MGAM) polypeptide or mRNA encoding an MGAM polypeptide, (16) an altered level of a phospholipase A2 receptor 1 (PLA2R1) polypeptide or mRNA encoding an PLA2R1 polypeptide, (17) an altered level of a transient receptor potential cation channel subfamily M member 1 (TRPM1) polypeptide or mRNA encoding an TRPM1 polypeptide, and (18) an altered level of a zinc finger protein 750 (ZNF750) polypeptide or mRNA encoding an ZNF750 polypeptide; Attorney Docket No.07039-2153WO1 / 2022-168 (b) classifying said cSCC as being likely to metastasize if said presence is determined; and (c) classifying said cSCC as not being likely to metastasize if said absence of each of (1)-(18) is determined. 75. The method of claim 74, wherein said mammal is a human. 76. The method of any one of claims 74-75, wherein the presence or absence of said altered level of said AOX1 polypeptide is determined. 77. The method of any one of claims 74-75, wherein the presence or absence of said altered level of said CALCOCO1 polypeptide is determined. 78. The method of any one of claims 74-75, wherein the presence or absence of said altered level of said CASP14 polypeptide is determined. 79. The method of any one of claims 74-75, wherein the presence or absence of said altered level of said CDC6 polypeptide is determined. 80. The method of any one of claims 74-75, wherein the presence or absence of said altered level of said CERS3 polypeptide is determined. 81. The method of any one of claims 74-75, wherein the presence or absence of said altered level of said CYP2E1 polypeptide is determined. 82. The method of any one of claims 74-75, wherein the presence or absence of said altered level of said CYP2U1 polypeptide is determined. 83. The method of any one of claims 74-75, wherein the presence or absence of said altered level of said CYP4F22 polypeptide is determined. Attorney Docket No.07039-2153WO1 / 2022-168 84. The method of any one of claims 74-75, wherein the presence or absence of said altered level of said CYP4F3 polypeptide is determined. 85. The method of any one of claims 74-75, wherein the presence or absence of said altered level of said DMD polypeptide is determined. 86. The method of any one of claims 74-75, wherein the presence or absence of said altered level of said EVPL polypeptide is determined. 87. The method of any one of claims 74-75, wherein the presence or absence of said altered level of said FASN polypeptide is determined. 88. The method of any one of claims 74-75, wherein the presence or absence of said altered level of said FN1 polypeptide is determined. 89. The method of any one of claims 74-75, wherein the presence or absence of said altered level of said KIT polypeptide is determined. 90. The method of any one of claims 74-75, wherein the presence or absence of said altered level of said MGAM polypeptide is determined. 91. The method of any one of claims 74-75, wherein the presence or absence of said altered level of said PLA2R1 polypeptide is determined. 92. The method of any one of claims 74-75, wherein the presence or absence of said altered level of said TRPM1 polypeptide is determined. 93. The method of any one of claims 74-75, wherein the presence or absence of said altered level of said ZNF750 polypeptide is determined. Attorney Docket No.07039-2153WO1 / 2022-168 94. The method of any one of claims 74-93, wherein said sample is a tissue sample comprising a cSCC cell. 95. A method for selecting a treatment for a mammal having a cSCC, wherein said method comprises: (a) determining that a sample from said mammal contains: the absence of (a-1) an altered level of an ACSL1 polypeptide or mRNA encoding an ACSL1 polypeptide, (a-2) an altered level of an ALDH1A1 polypeptide or mRNA encoding an ALDH1A1 polypeptide, (a-3) an altered level of an ALDH3A2 polypeptide or mRNA encoding an ALDH3A2 polypeptide, (a-4) an altered level of an ALOX12 polypeptide or mRNA encoding an ALOX12 polypeptide, (a-5) an altered level of a CALCOCO1 polypeptide or mRNA encoding a CALCOCO1 polypeptide, (a-6) an altered level of a CASP14 polypeptide or mRNA encoding a CASP14 polypeptide, (a-7) an altered level of a CDC6 polypeptide or mRNA encoding a CDC6 polypeptide, (a-8) an altered level of a CDCA5 polypeptide or mRNA encoding a CDCA5 polypeptide, (a-9) an altered level of a CEP55 polypeptide or mRNA encoding a CEP55 polypeptide, (a-10) an altered level of a CXCL8 polypeptide or mRNA encoding a CXCL8 polypeptide, (a-11) an altered level of a CYP4F3 polypeptide or mRNA encoding a CYP4F3 polypeptide, (a-12) an altered level of a DMD polypeptide or mRNA encoding a DMD polypeptide, (a-13) an altered level of a KRT2 polypeptide or mRNA encoding a KRT2 polypeptide, (a-14) an altered level of a NQO1 polypeptide or mRNA encoding a NQO1 polypeptide, (a-15) an altered level of a PRC1 polypeptide or mRNA encoding a PRC1 polypeptide, (a-16) an altered level of a TSGA10 polypeptide or mRNA encoding a TSGA10 polypeptide, and (a-17) an altered level of a ZNF750 polypeptide or mRNA encoding a ZNF750 polypeptide; or the presence of at least one of (a-18) an altered level of a CYP2U1 polypeptide or mRNA encoding a CYP2U1 polypeptide, (a-19) an altered level of a CASP14 polypeptide or mRNA encoding a CASP14 polypeptide, (a-20) an altered level of a CDC6 polypeptide or mRNA encoding a CDC6 polypeptide, (a-21) an altered level of a FN1 polypeptide or mRNA encoding a FN1 polypeptide, (a-22) an altered level of a MGAM polypeptide or mRNA Attorney Docket No.07039-2153WO1 / 2022-168 encoding a MGAM polypeptide, (a-23) an altered level of an EVPL polypeptide or mRNA encoding an EVPL polypeptide, (a-24) an altered level of an AOX1 polypeptide or mRNA encoding an AOX1 polypeptide, (a-25) an altered level of a PLA2R1 polypeptide or mRNA encoding a PLA2R1 polypeptide, (a-26) an altered level of a TRPM1 polypeptide or mRNA encoding a TRPM1 polypeptide, (a-27) an altered level of a DMD polypeptide or mRNA encoding a DMD polypeptide, (a-28) an altered level of a CYP4F22 polypeptide or mRNA encoding a CYP4F22 polypeptide, (a-29) an altered level of a CERS3 polypeptide or mRNA encoding a CERS3 polypeptide, (a-30) an altered level of a KIT polypeptide or mRNA encoding a KIT polypeptide, (a-31) an altered level of a ZNF750 polypeptide or mRNA encoding a ZNF750 polypeptide, (a-32) an altered level of a CYP4F3 polypeptide or mRNA encoding a CYP4F3 polypeptide, (a-33) an altered level of a CYP4F3 polypeptide or mRNA encoding a CYP4F3 polypeptide, (a-34) an altered level of a CALCOCO1 polypeptide or mRNA encoding a CALCOCO1 polypeptide, (a-27) an altered level of a CYP2E1 polypeptide or mRNA encoding a CYP2E1 polypeptide, and (a-35) an altered level of a FASN polypeptide or mRNA encoding a FASN polypeptide; and (b) selecting said mammal for surgery to remove said cSCC and to receive an adjuvant therapy. 96. A method for selecting a treatment for a mammal having a cSCC, wherein said method comprises: (a) determining that a sample from said mammal contains: the presence of at least one of (a-1) an altered level of an ACSL1 polypeptide or mRNA encoding an ACSL1 polypeptide, (a-2) an altered level of an ALDH1A1 polypeptide or mRNA encoding an ALDH1A1 polypeptide, (a-3) an altered level of an ALDH3A2 polypeptide or mRNA encoding an ALDH3A2 polypeptide, (a-4) an altered level of an ALOX12 polypeptide or mRNA encoding an ALOX12 polypeptide, (a-5) an altered level of a CALCOCO1 polypeptide or mRNA encoding a CALCOCO1 polypeptide, (a-6) an altered level of a CASP14 polypeptide or mRNA encoding a CASP14 polypeptide, (a-7) an altered level of a CDC6 polypeptide or mRNA encoding a CDC6 polypeptide, (a-8) an altered level of a CDCA5 polypeptide or mRNA encoding a CDCA5 polypeptide, (a-9) an altered level of Attorney Docket No.07039-2153WO1 / 2022-168 a CEP55 polypeptide or mRNA encoding a CEP55 polypeptide, (a-10) an altered level of a CXCL8 polypeptide or mRNA encoding a CXCL8 polypeptide, (a-11) an altered level of a CYP4F3 polypeptide or mRNA encoding a CYP4F3 polypeptide, (a-12) an altered level of a DMD polypeptide or mRNA encoding a DMD polypeptide, (a-13) an altered level of a KRT2 polypeptide or mRNA encoding a KRT2 polypeptide, (a-14) an altered level of a NQO1 polypeptide or mRNA encoding a NQO1 polypeptide, (a-15) an altered level of a PRC1 polypeptide or mRNA encoding a PRC1 polypeptide, (a-16) an altered level of a TSGA10 polypeptide or mRNA encoding a TSGA10 polypeptide, and (a-17) an altered level of a ZNF750 polypeptide or mRNA encoding a ZNF750 polypeptide; or the absence of (a-18) an altered level of a CYP2U1 polypeptide or mRNA encoding a CYP2U1 polypeptide, (a-19) an altered level of a CASP14 polypeptide or mRNA encoding a CASP14 polypeptide, (a-20) an altered level of a CDC6 polypeptide or mRNA encoding a CDC6 polypeptide, (a-21) an altered level of a FN1 polypeptide or mRNA encoding a FN1 polypeptide, (a-22) an altered level of a MGAM polypeptide or mRNA encoding a MGAM polypeptide, (a-23) an altered level of an EVPL polypeptide or mRNA encoding an EVPL polypeptide, (a-24) an altered level of an AOX1 polypeptide or mRNA encoding an AOX1 polypeptide, (a-25) an altered level of a PLA2R1 polypeptide or mRNA encoding a PLA2R1 polypeptide, (a-26) an altered level of a TRPM1 polypeptide or mRNA encoding a TRPM1 polypeptide, (a-27) an altered level of a DMD polypeptide or mRNA encoding a DMD polypeptide, (a-28) an altered level of a CYP4F22 polypeptide or mRNA encoding a CYP4F22 polypeptide, (a-29) an altered level of a CERS3 polypeptide or mRNA encoding a CERS3 polypeptide, (a-30) an altered level of a KIT polypeptide or mRNA encoding a KIT polypeptide, (a-31) an altered level of a ZNF750 polypeptide or mRNA encoding a ZNF750 polypeptide, (a-32) an altered level of a CYP4F3 polypeptide or mRNA encoding a CYP4F3 polypeptide, (a-33) an altered level of a CYP4F3 polypeptide or mRNA encoding a CYP4F3 polypeptide, (a-34) an altered level of a CALCOCO1 polypeptide or mRNA encoding a CALCOCO1 polypeptide, (a-35) an altered level of a CYP2E1 polypeptide or mRNA encoding a CYP2E1 polypeptide, and (a-36) an altered level of a FASN polypeptide or mRNA encoding a FASN polypeptide; and Attorney Docket No.07039-2153WO1 / 2022-168 (b) selecting said mammal for surgery to remove said cSCC in the absence of an adjuvant therapy. 97. The method of any one of claims 95-96, wherein said mammal is a human. 98. The method of any one of claims 95-97, wherein said adjuvant therapy comprises radiation therapy. 99. The method of any one of claims 95-98, wherein said adjuvant therapy comprises administering an anti-cancer drug to said mammal. 100. The method of claim 99, wherein said anti-cancer drug is selected from the group consisting of cemiplimab-rwlc, nivolumab, ipilimumab, pembrolizumab, talimogene laherparepvec, cetuximab, capecitabine, carboplatin, and fluorouracil (5-FU). 101. A method for treating a mammal having a cSCC, wherein said method comprises: (a) determining that a sample from said mammal contains: the absence of (a-1) an altered level of an ACSL1 polypeptide or mRNA encoding an ACSL1 polypeptide, (a-2) an altered level of an ALDH1A1 polypeptide or mRNA encoding an ALDH1A1 polypeptide, (a-3) an altered level of an ALDH3A2 polypeptide or mRNA encoding an ALDH3A2 polypeptide, (a-4) an altered level of an ALOX12 polypeptide or mRNA encoding an ALOX12 polypeptide, (a-5) an altered level of a CALCOCO1 polypeptide or mRNA encoding a CALCOCO1 polypeptide, (a-6) an altered level of a CASP14 polypeptide or mRNA encoding a CASP14 polypeptide, (a-7) an altered level of a CDC6 polypeptide or mRNA encoding a CDC6 polypeptide, (a-8) an altered level of a CDCA5 polypeptide or mRNA encoding a CDCA5 polypeptide, (a-9) an altered level of a CEP55 polypeptide or mRNA encoding a CEP55 polypeptide, (a-10) an altered level of a CXCL8 polypeptide or mRNA encoding a CXCL8 polypeptide, (a-11) an altered level of a CYP4F3 polypeptide or mRNA encoding a CYP4F3 polypeptide, (a-12) an altered level of a DMD polypeptide or mRNA encoding a DMD polypeptide, (a-13) an altered level of a KRT2 Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide or mRNA encoding a KRT2 polypeptide, (a-14) an altered level of a NQO1 polypeptide or mRNA encoding a NQO1 polypeptide, (a-15) an altered level of a PRC1 polypeptide or mRNA encoding a PRC1 polypeptide, (a-16) an altered level of a TSGA10 polypeptide or mRNA encoding a TSGA10 polypeptide, and (a-17) an altered level of a ZNF750 polypeptide or mRNA encoding a ZNF750 polypeptide; or the presence of at least one of (a-18) an altered level of a CYP2U1 polypeptide or mRNA encoding a CYP2U1 polypeptide, (a-19) an altered level of a CASP14 polypeptide or mRNA encoding a CASP14 polypeptide, (a-20) an altered level of a CDC6 polypeptide or mRNA encoding a CDC6 polypeptide, (a-21) an altered level of a FN1 polypeptide or mRNA encoding a FN1 polypeptide, (a-22) an altered level of a MGAM polypeptide or mRNA encoding a MGAM polypeptide, (a-23) an altered level of an EVPL polypeptide or mRNA encoding an EVPL polypeptide, (a-24) an altered level of an AOX1 polypeptide or mRNA encoding an AOX1 polypeptide, (a-25) an altered level of a PLA2R1 polypeptide or mRNA encoding a PLA2R1 polypeptide, (a-26) an altered level of a TRPM1 polypeptide or mRNA encoding a TRPM1 polypeptide, (a-27) an altered level of a DMD polypeptide or mRNA encoding a DMD polypeptide, (a-28) an altered level of a CYP4F22 polypeptide or mRNA encoding a CYP4F22 polypeptide, (a-29) an altered level of a CERS3 polypeptide or mRNA encoding a CERS3 polypeptide, (a-30) an altered level of a KIT polypeptide or mRNA encoding a KIT polypeptide, (a-31) an altered level of a ZNF750 polypeptide or mRNA encoding a ZNF750 polypeptide, (a-32) an altered level of a CYP4F3 polypeptide or mRNA encoding a CYP4F3 polypeptide, (a-33) an altered level of a CYP4F3 polypeptide or mRNA encoding a CYP4F3 polypeptide, (a-34) an altered level of a CALCOCO1 polypeptide or mRNA encoding a CALCOCO1 polypeptide, (a-35) an altered level of a CYP2E1 polypeptide or mRNA encoding a CYP2E1 polypeptide, and (a-36) an altered level of a FASN polypeptide or mRNA encoding a FASN polypeptide; (b) subjecting said mammal to a surgery to remove said cSCC; and (c) administering an adjuvant therapy to said mammal. 102. A method for treating a cSCC, wherein said method comprises subjecting a mammal identified as having a sample comprising (a) or (b) to a surgery to remove said cSCC and Attorney Docket No.07039-2153WO1 / 2022-168 administering an adjuvant therapy to said mammal, wherein said (a) comprises the absence of (a-1) an altered level of an ACSL1 polypeptide or mRNA encoding an ACSL1 polypeptide, (a-2) an altered level of an ALDH1A1 polypeptide or mRNA encoding an ALDH1A1 polypeptide, (a-3) an altered level of an ALDH3A2 polypeptide or mRNA encoding an ALDH3A2 polypeptide, (a-4) an altered level of an ALOX12 polypeptide or mRNA encoding an ALOX12 polypeptide, (a-5) an altered level of a CALCOCO1 polypeptide or mRNA encoding a CALCOCO1 polypeptide, (a-6) an altered level of a CASP14 polypeptide or mRNA encoding a CASP14 polypeptide, (a-7) an altered level of a CDC6 polypeptide or mRNA encoding a CDC6 polypeptide, (a-8) an altered level of a CDCA5 polypeptide or mRNA encoding a CDCA5 polypeptide, (a-9) an altered level of a CEP55 polypeptide or mRNA encoding a CEP55 polypeptide, (a-10) an altered level of a CXCL8 polypeptide or mRNA encoding a CXCL8 polypeptide, (a-11) an altered level of a CYP4F3 polypeptide or mRNA encoding a CYP4F3 polypeptide, (a-12) an altered level of a DMD polypeptide or mRNA encoding a DMD polypeptide, (a-13) an altered level of a KRT2 polypeptide or mRNA encoding a KRT2 polypeptide, (a-14) an altered level of a NQO1 polypeptide or mRNA encoding a NQO1 polypeptide, (a-15) an altered level of a PRC1 polypeptide or mRNA encoding a PRC1 polypeptide, (a-16) an altered level of a TSGA10 polypeptide or mRNA encoding a TSGA10 polypeptide, and (a-17) an altered level of a ZNF750 polypeptide or mRNA encoding a ZNF750 polypeptide, and wherein said (b) comprises the presence of at least one of (b-1) an altered level of a CYP2U1 polypeptide or mRNA encoding a CYP2U1 polypeptide, (b-2) an altered level of a CASP14 polypeptide or mRNA encoding a CASP14 polypeptide, (b-3) an altered level of a CDC6 polypeptide or mRNA encoding a CDC6 polypeptide, (b-4) an altered level of a FN1 polypeptide or mRNA encoding a FN1 polypeptide, (b-5) an altered level of a MGAM polypeptide or mRNA encoding a MGAM polypeptide, (b-6) an altered level of an EVPL polypeptide or mRNA encoding an EVPL polypeptide, (b-7) an altered level of an AOX1 polypeptide or mRNA encoding an AOX1 polypeptide, (b-8) an altered level of a PLA2R1 polypeptide or mRNA encoding a PLA2R1 polypeptide, (b-9) an altered level of a TRPM1 polypeptide or mRNA encoding a TRPM1 polypeptide, (b-10) an altered level of a DMD polypeptide or mRNA encoding a DMD polypeptide, (b-11) an altered level of a CYP4F22 polypeptide or mRNA Attorney Docket No.07039-2153WO1 / 2022-168 encoding a CYP4F22 polypeptide, (b-12) an altered level of a CERS3 polypeptide or mRNA encoding a CERS3 polypeptide, (b-13) an altered level of a KIT polypeptide or mRNA encoding a KIT polypeptide, (b-14) an altered level of a ZNF750 polypeptide or mRNA encoding a ZNF750 polypeptide, (b-15) an altered level of a CYP4F3 polypeptide or mRNA encoding a CYP4F3 polypeptide, (b-16) an altered level of a CYP4F3 polypeptide or mRNA encoding a CYP4F3 polypeptide, (b-17) an altered level of a CALCOCO1 polypeptide or mRNA encoding a CALCOCO1 polypeptide, (b-18) an altered level of a CYP2E1 polypeptide or mRNA encoding a CYP2E1 polypeptide, and (b-19) an altered level of a FASN polypeptide or mRNA encoding a FASN polypeptide. 103. The method of any one of claims 101-102, wherein said mammal is a human. 104. The method of any one of claims 101-103, wherein said sample is a tissue sample comprising a cSCC cell. 105. The method of any one of claims 101-104, wherein said adjuvant therapy comprises radiation therapy. 106. The method of any one of claims 101-105, wherein said adjuvant therapy comprises administering an anti-cancer drug to said mammal. 107. The method of claim 106, wherein said anti-cancer drug is selected from the group consisting of cemiplimab-rwlc, nivolumab, ipilimumab, pembrolizumab, talimogene laherparepvec, cetuximab, capecitabine, carboplatin, and 5-FU. 108. A method for treating a mammal having a cSCC, wherein said method comprises: (a) determining if a sample from said mammal comprises: the presence of at least one of (a-1) an altered level of an ACSL1 polypeptide or mRNA encoding an ACSL1 polypeptide, (a-2) an altered level of an ALDH1A1 polypeptide or mRNA encoding an ALDH1A1 polypeptide, (a-3) an altered level of an ALDH3A2 Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide or mRNA encoding an ALDH3A2 polypeptide, (a-4) an altered level of an ALOX12 polypeptide or mRNA encoding an ALOX12 polypeptide, (a-5) an altered level of a CALCOCO1 polypeptide or mRNA encoding a CALCOCO1 polypeptide, (a-6) an altered level of a CASP14 polypeptide or mRNA encoding a CASP14 polypeptide, (a-7) an altered level of a CDC6 polypeptide or mRNA encoding a CDC6 polypeptide, (a-8) an altered level of a CDCA5 polypeptide or mRNA encoding a CDCA5 polypeptide, (a-9) an altered level of a CEP55 polypeptide or mRNA encoding a CEP55 polypeptide, (a-10) an altered level of a CXCL8 polypeptide or mRNA encoding a CXCL8 polypeptide, (a-11) an altered level of a CYP4F3 polypeptide or mRNA encoding a CYP4F3 polypeptide, (a-12) an altered level of a DMD polypeptide or mRNA encoding a DMD polypeptide, (a-13) an altered level of a KRT2 polypeptide or mRNA encoding a KRT2 polypeptide, (a-14) an altered level of a NQO1 polypeptide or mRNA encoding a NQO1 polypeptide, (a-15) an altered level of a PRC1 polypeptide or mRNA encoding a PRC1 polypeptide, (a-16) an altered level of a TSGA10 polypeptide or mRNA encoding a TSGA10 polypeptide, and (a-17) an altered level of a ZNF750 polypeptide or mRNA encoding a ZNF750 polypeptide; or the absence of (a-18) an altered level of a CYP2U1 polypeptide or mRNA encoding a CYP2U1 polypeptide, (a-19) an altered level of a CASP14 polypeptide or mRNA encoding a CASP14 polypeptide, (a-20) an altered level of a CDC6 polypeptide or mRNA encoding a CDC6 polypeptide, (a-21) an altered level of a FN1 polypeptide or mRNA encoding a FN1 polypeptide, (a-22) an altered level of a MGAM polypeptide or mRNA encoding a MGAM polypeptide, (a-23) an altered level of an EVPL polypeptide or mRNA encoding an EVPL polypeptide, (a-24) an altered level of an AOX1 polypeptide or mRNA encoding an AOX1 polypeptide, (a-25) an altered level of a PLA2R1 polypeptide or mRNA encoding a PLA2R1 polypeptide, (a-26) an altered level of a TRPM1 polypeptide or mRNA encoding a TRPM1 polypeptide, (a-27) an altered level of a DMD polypeptide or mRNA encoding a DMD polypeptide, (a-28) an altered level of a CYP4F22 polypeptide or mRNA encoding a CYP4F22 polypeptide, (a-29) an altered level of a CERS3 polypeptide or mRNA encoding a CERS3 polypeptide, (a-30) an altered level of a KIT polypeptide or mRNA encoding a KIT polypeptide, (a-31) an altered level of a ZNF750 polypeptide or mRNA encoding a ZNF750 polypeptide, (a-32) an altered level of a CYP4F3 polypeptide or mRNA encoding a CYP4F3 Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide, (a-33) an altered level of a CYP4F3 polypeptide or mRNA encoding a CYP4F3 polypeptide, (a-34) an altered level of a CALCOCO1 polypeptide or mRNA encoding a CALCOCO1 polypeptide, (a-27) an altered level of a CYP2E1 polypeptide or mRNA encoding a CYP2E1 polypeptide, and (a-35) an altered level of a FASN polypeptide or mRNA encoding a FASN polypeptide; and (b) subjecting said mammal to a surgery to remove said cSCC in the absence of an adjuvant therapy. 109. A method for treating cSCC, wherein said method comprises subjecting a mammal identified as comprising a sample comprising (a) or (b) to a surgery to remove said cSCC in the absence of an adjuvant therapy, wherein said (a) comprises the presence of at least one of (a-1) an altered level of an ACSL1 polypeptide or mRNA encoding an ACSL1 polypeptide, (a-2) an altered level of an ALDH1A1 polypeptide or mRNA encoding an ALDH1A1 polypeptide, (a-3) an altered level of an ALDH3A2 polypeptide or mRNA encoding an ALDH3A2 polypeptide, (a-4) an altered level of an ALOX12 polypeptide or mRNA encoding an ALOX12 polypeptide, (a-5) an altered level of a CALCOCO1 polypeptide or mRNA encoding a CALCOCO1 polypeptide, (a-6) an altered level of a CASP14 polypeptide or mRNA encoding a CASP14 polypeptide, (a-7) an altered level of a CDC6 polypeptide or mRNA encoding a CDC6 polypeptide, (a-8) an altered level of a CDCA5 polypeptide or mRNA encoding a CDCA5 polypeptide, (a-9) an altered level of a CEP55 polypeptide or mRNA encoding a CEP55 polypeptide, (a-10) an altered level of a CXCL8 polypeptide or mRNA encoding a CXCL8 polypeptide, (a-11) an altered level of a CYP4F3 polypeptide or mRNA encoding a CYP4F3 polypeptide, (a-12) an altered level of a DMD polypeptide or mRNA encoding a DMD polypeptide, (a-13) an altered level of a KRT2 polypeptide or mRNA encoding a KRT2 polypeptide, (a-14) an altered level of a NQO1 polypeptide or mRNA encoding a NQO1 polypeptide, (a-15) an altered level of a PRC1 polypeptide or mRNA encoding a PRC1 polypeptide, (a-16) an altered level of a TSGA10 polypeptide or mRNA encoding a TSGA10 polypeptide, and (a-17) an altered level of a ZNF750 polypeptide or mRNA encoding a ZNF750 polypeptide, and wherein said (b) comprises the absence of (b-1) an altered level of a CSAG1 polypeptide or mRNA encoding a CSAG1 Attorney Docket No.07039-2153WO1 / 2022-168 polypeptide, (b-2) an altered level of an UBE2C polypeptide or mRNA encoding an UBE2C polypeptide, (b-3) an altered level of an ANKRD1 polypeptide or mRNA encoding an ANKRD1 polypeptide, (b-4) an altered level of a CSMD3 polypeptide or mRNA encoding a CSMD3 polypeptide, (b-5) an altered level of a TOP2A polypeptide or mRNA encoding a TOP2A polypeptide, (b-6) an altered level of a TPX2 polypeptide or mRNA encoding a TPX2 polypeptide, (b-7) an altered level of a KSR2 polypeptide or mRNA encoding a KSR2 polypeptide, (b-8) an altered level of a CSMD2 polypeptide or mRNA encoding a CSMD2 polypeptide, (b-9) an altered level of a MMP20 polypeptide or mRNA encoding a MMP20 polypeptide, (b-10) an altered level of a PCSK1 polypeptide or mRNA encoding a PCSK1 polypeptide, (b-11) an altered level of a TMEM150B polypeptide or mRNA encoding a TMEM150B polypeptide, (b-12) an altered level of an ACSL1 polypeptide or mRNA encoding an ACSL1 polypeptide, (b-13) an altered level of a TSGA10 polypeptide or mRNA encoding a TSGA10 polypeptide, (b-14) an altered level of a KIT polypeptide or mRNA encoding a KIT polypeptide, (b-15) an altered level of a RGL3 polypeptide or mRNA encoding a RGL3 polypeptide, and (b-16) an altered level of a PLA2G6 polypeptide or mRNA encoding a PLA2G6 polypeptide. 110. The method of any one of claims 108-109, wherein said mammal is a human. 111. The method of any one of claims 108-110, wherein said sample is a tissue sample comprising a cSCC cell. 112. The method of any one of claims 108-111, wherein said adjuvant therapy comprises radiation therapy. 113. The method of any one of claims 108-112, wherein said adjuvant therapy comprises administering an anti-cancer drug to said mammal. Attorney Docket No.07039-2153WO1 / 2022-168 114. The method of claim 113, wherein said anti-cancer drug is selected from the group consisting of cemiplimab-rwlc, nivolumab, ipilimumab, pembrolizumab, talimogene laherparepvec, cetuximab, capecitabine, carboplatin, and 5-FU.
PCT/US2023/078902 2022-11-07 2023-11-07 Methods and materials for assessing and treating cutaneous squamous cell carcinoma WO2024102702A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202263423254P 2022-11-07 2022-11-07
US63/423,254 2022-11-07

Publications (3)

Publication Number Publication Date
WO2024102702A2 true WO2024102702A2 (en) 2024-05-16
WO2024102702A3 WO2024102702A3 (en) 2024-07-11
WO2024102702A9 WO2024102702A9 (en) 2024-08-22

Family

ID=91033450

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2023/078902 WO2024102702A2 (en) 2022-11-07 2023-11-07 Methods and materials for assessing and treating cutaneous squamous cell carcinoma

Country Status (1)

Country Link
WO (1) WO2024102702A2 (en)

Also Published As

Publication number Publication date
WO2024102702A3 (en) 2024-07-11
WO2024102702A9 (en) 2024-08-22

Similar Documents

Publication Publication Date Title
JP7401710B2 (en) System and method for identifying cancer treatment from normalized biomarker scores
JP5457630B2 (en) Tape stripping method for analyzing skin diseases and pathological skin conditions
Oestreicher et al. Molecular classification of psoriasis disease-associated genes through pharmacogenomic expression profiling
EP2885426B1 (en) Systems, models and methods for identifying and evaluating skin-active agents effective for treating an array of skin disorders
JP5841234B2 (en) Systems, models, and methods for identifying and evaluating skin active agents effective in the treatment of dandruff / seborrheic dermatitis
EP2971156B1 (en) Genes and gene signatures for diagnosis and treatment of melanoma
US12000003B2 (en) Platform and sample type independent single sample classifier for treatment decision making in pancreatic ductal adenocarcinoma cancer
WO2022192457A1 (en) Predicting response to treatments in patients with clear cell renal cell carcinoma
McLoughlin et al. Limited dynamic range of immune response gene expression observed in healthy blood donors using RT-PCR
EP3666906A1 (en) Methods and kits for the prognosis of squamous cell carcinomas (scc)
Hu et al. Establishment and validation of psoriasis evaluation models
WO2024102702A2 (en) Methods and materials for assessing and treating cutaneous squamous cell carcinoma
US20220290254A1 (en) B cell-enriched tumor microenvironments
CN114354943A (en) Immune therapy efficacy prediction marker and prediction model construction and application
Sun et al. Identification of key candidate genes and pathways for relationship between ovarian cancer and diabetes mellitus using bioinformatical analysis
US20210102260A1 (en) Patient classification and prognositic method
AU2022405276A1 (en) Assessing and treating melanoma
CA3240376A1 (en) Assessing and treating melanoma
US20230295727A1 (en) Biomarkers for the Diagnosis of Parkinson&#39;s Disease
US20210317537A1 (en) Novel mrna based prognostic index derived from differential expression analysis improves overall survival estimates in glioblastoma
Hinchcliff et al. Molecular stratification by gene expression as a paradigm for precision medicine in systemic sclerosis
Zhu et al. Gene expression profiles following active HE4 stimulation in epithelial ovarian cancer cells: microarray study and comprehensive bioinformatics analysis
Murphy et al. Non-invasive epidermal proteome assessment-based diagnosis and molecular subclassification of psoriasis and eczematous dermatitis
WO2023089146A1 (en) Prognostic and treatment response predictive method
WO2024216069A1 (en) Pan-cancer tumor microenvironment classification based on immune escape mechanisms and immune infiltration

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 23889578

Country of ref document: EP

Kind code of ref document: A2