CN116716404B - Device for distinguishing ovarian clear cell carcinoma from high-grade serous carcinoma based on S100A2 - Google Patents
Device for distinguishing ovarian clear cell carcinoma from high-grade serous carcinoma based on S100A2 Download PDFInfo
- Publication number
- CN116716404B CN116716404B CN202310697259.5A CN202310697259A CN116716404B CN 116716404 B CN116716404 B CN 116716404B CN 202310697259 A CN202310697259 A CN 202310697259A CN 116716404 B CN116716404 B CN 116716404B
- Authority
- CN
- China
- Prior art keywords
- sample
- detection kit
- carcinoma
- expression level
- clear cell
- Prior art date
- Legal status (The legal status 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 status listed.)
- Active
Links
- 201000003707 ovarian clear cell carcinoma Diseases 0.000 title abstract description 54
- 208000004548 serous cystadenocarcinoma Diseases 0.000 title abstract description 4
- 230000014509 gene expression Effects 0.000 claims abstract description 37
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 17
- 201000011510 cancer Diseases 0.000 claims abstract description 9
- 206010033128 Ovarian cancer Diseases 0.000 claims description 23
- 238000001514 detection method Methods 0.000 claims description 23
- 108090000623 proteins and genes Proteins 0.000 claims description 14
- 102000004169 proteins and genes Human genes 0.000 claims description 9
- 239000003153 chemical reaction reagent Substances 0.000 claims description 7
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 6
- 238000001574 biopsy Methods 0.000 claims description 6
- 238000003757 reverse transcription PCR Methods 0.000 claims description 5
- 238000000018 DNA microarray Methods 0.000 claims description 4
- 108020004999 messenger RNA Proteins 0.000 claims description 4
- 238000013115 immunohistochemical detection Methods 0.000 claims description 3
- 238000002965 ELISA Methods 0.000 claims description 2
- 208000016632 ovarian clear cell cancer Diseases 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 2
- 210000004027 cell Anatomy 0.000 description 24
- 239000000523 sample Substances 0.000 description 20
- 210000001519 tissue Anatomy 0.000 description 13
- 208000007571 Ovarian Epithelial Carcinoma Diseases 0.000 description 10
- 230000006870 function Effects 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 238000011532 immunohistochemical staining Methods 0.000 description 5
- 208000030070 Malignant epithelial tumor of ovary Diseases 0.000 description 4
- 206010061328 Ovarian epithelial cancer Diseases 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 238000012163 sequencing technique Methods 0.000 description 4
- 210000001124 body fluid Anatomy 0.000 description 3
- 239000010839 body fluid Substances 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 238000003559 RNA-seq method Methods 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 210000003722 extracellular fluid Anatomy 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 230000036210 malignancy Effects 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000002552 multiple reaction monitoring Methods 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 238000000513 principal component analysis Methods 0.000 description 2
- 238000003753 real-time PCR Methods 0.000 description 2
- 210000003296 saliva Anatomy 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000012800 visualization Methods 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 201000009273 Endometriosis Diseases 0.000 description 1
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 101710088172 HTH-type transcriptional regulator RipA Proteins 0.000 description 1
- 102100022123 Hepatocyte nuclear factor 1-beta Human genes 0.000 description 1
- 101001045758 Homo sapiens Hepatocyte nuclear factor 1-beta Proteins 0.000 description 1
- 206010036790 Productive cough Diseases 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 208000034841 Thrombotic Microangiopathies Diseases 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000001772 blood platelet Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 239000011651 chromium Substances 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000010219 correlation analysis Methods 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000001378 electrochemiluminescence detection Methods 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 210000001723 extracellular space Anatomy 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 210000003731 gingival crevicular fluid Anatomy 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 238000012165 high-throughput sequencing Methods 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 230000002055 immunohistochemical effect Effects 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- JMANVNJQNLATNU-UHFFFAOYSA-N oxalonitrile Chemical compound N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 description 1
- 238000009595 pap smear Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 238000011518 platinum-based chemotherapy Methods 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000010814 radioimmunoprecipitation assay Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 239000004065 semiconductor Substances 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 238000012174 single-cell RNA sequencing Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 210000003802 sputum Anatomy 0.000 description 1
- 208000024794 sputum Diseases 0.000 description 1
- 210000004243 sweat Anatomy 0.000 description 1
- 210000001179 synovial fluid Anatomy 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
Classifications
-
- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
- G16B25/00—ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
- G16B25/20—Polymerase chain reaction [PCR]; Primer or probe design; Probe optimisation
-
- 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
-
- 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
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57407—Specifically defined cancers
-
- 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
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57407—Specifically defined cancers
- G01N33/57449—Specifically defined cancers of ovaries
-
- 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
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
-
- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
- G16B45/00—ICT specially adapted for bioinformatics-related data visualisation, e.g. displaying of maps or networks
-
- 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
- C12Q2600/112—Disease subtyping, staging or classification
-
- 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
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/46—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans from vertebrates
- G01N2333/47—Assays involving proteins of known structure or function as defined in the subgroups
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A90/00—Technologies having an indirect contribution to adaptation to climate change
- Y02A90/10—Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Physics & Mathematics (AREA)
- Biotechnology (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- General Health & Medical Sciences (AREA)
- Analytical Chemistry (AREA)
- Pathology (AREA)
- Cell Biology (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Oncology (AREA)
- Hospice & Palliative Care (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- General Physics & Mathematics (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Food Science & Technology (AREA)
- Organic Chemistry (AREA)
- Biophysics (AREA)
- Medical Informatics (AREA)
- Evolutionary Biology (AREA)
- Bioinformatics & Computational Biology (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Theoretical Computer Science (AREA)
- General Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Data Mining & Analysis (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
The invention belongs to the field of biological medicine, and particularly relates to a device for distinguishing ovarian clear cell carcinoma from high-grade serous carcinoma based on S100A 2. In particular, the present invention provides an apparatus for determining a cancer type, the apparatus comprising: a memory and a processor; the memory is used for storing program instructions; the processor is configured to invoke program instructions that, when executed, are configured to: S100A2 expression data of the sample to be detected are obtained, and the typing result of the sample to be detected is judged by comparing the S100A2 expression data with a threshold value.
Description
Technical Field
The invention belongs to the field of biological medicine, and particularly relates to equipment for distinguishing ovarian clear cell carcinoma from high-grade serous carcinoma based on S100A 2.
Background
Ovarian epithelial cancer (epithelial ovarian carcinoma, EOC) is one of the most common gynaecological malignancies in women, with the incidence being the seventh among female malignancies. Of these, high-grade serous ovarian cancer (High-grade serous ovarian cancer, HGSC) is the most common, accounting for about 60% of ovarian epithelial cancers. Ovarian clear cell carcinoma (Ovarian clear cell carcinoma, OCCC) is the second leading stage, accounting for about 5-11% of ovarian epithelial cancers.
There are differences in the demographic, morphological and molecular characteristics of Ovarian Clear Cell Carcinoma (OCCC) and high grade serous ovarian carcinoma (HGSC). Ovarian Clear Cell Carcinoma (OCCC) is more prevalent in asians than in other ethnicities, and is closely associated with endometriosis. Ovarian Clear Cell Carcinoma (OCCC) exists as tubular cystic structures and clear cells, and high grade serous ovarian carcinoma (HGSC) exists as solid and papillary structures. Ovarian Clear Cell Carcinoma (OCCC) is generally WT-1 and ER negative, napsin A and HNF1B positive. However, high grade serous ovarian cancer (HGSC) is generally WT-1 and ER positive, lacking expression of either Napsin A or HNF 1B.
Surgery in combination with subsequent chemotherapy is a conventional treatment for Ovarian Clear Cell Carcinoma (OCCC) and high grade serous ovarian carcinoma (HGSC). However, ovarian Clear Cell Carcinoma (OCCC) is resistant to conventional platinum-based chemotherapy and has poor prognosis compared to high grade serous ovarian carcinoma (HGSC). Thus, exploring the cellular and molecular differences in Ovarian Clear Cell Carcinoma (OCCC) and high grade serous ovarian carcinoma (HGSC) would help to find alternative therapies.
Disclosure of Invention
The invention provides a basis for screening differential genes of Ovarian Clear Cell Carcinoma (OCCC) and high-grade serous ovarian carcinoma (HGSC), collecting biopsy samples of patients with the Ovarian Clear Cell Carcinoma (OCCC) and the high-grade serous ovarian carcinoma (HGSC), performing scRNA-seq, and verifying the application value of the biomarker in distinguishing the Ovarian Clear Cell Carcinoma (OCCC) and the high-grade serous ovarian carcinoma (HGSC) through a database and clinical samples after screening the differential genes, and provides a basis for clinically distinguishing the patients with the Ovarian Clear Cell Carcinoma (OCCC) and the high-grade serous ovarian carcinoma (HGSC).
Specifically, the invention provides the following technical scheme:
in a first aspect, the present invention provides an apparatus for determining a cancer type, the apparatus comprising: a memory and a processor;
the memory is used for storing program instructions;
the processor is configured to invoke program instructions that, when executed, are configured to: S100A2 expression data of the sample to be detected are obtained, and the typing result of the sample to be detected is judged by comparing the S100A2 expression data with a threshold value.
More specifically, the typing result is that the sample to be tested is judged to be derived from an Ovarian Clear Cell Carcinoma (OCCC) patient or a high-grade serous ovarian carcinoma (HGSC) patient, and when the S100A2 expression data is lower than a threshold value, the sample to be tested is judged to be derived from the Ovarian Clear Cell Carcinoma (OCCC) patient, and when the S100A2 expression data is higher than the threshold value, the sample to be tested is judged to be derived from the high-grade serous ovarian carcinoma (HGSC) patient.
The threshold value is well known in the art and depends on the particular measurement technique, the determination of the threshold value is within the skill of the person skilled in the art.
As used herein, memory includes one or more of the following: a non-transitory computer readable medium, a magnetic disk or other magnetic storage medium, an optical disk or other optical storage medium, a Random Access Memory (RAM), a Read Only Memory (ROM) or other electronic memory device or chip, or a collection of chips that are operably interconnected; an internet/intranet server from which the stored instructions may be retrieved via an internet/intranet or local area network; etc. Exemplary include various memory disks, memory sticks, memory cards, memory modules, and the like.
As used herein, a processor includes one or more of a microprocessor, microcontroller, graphics Processing Unit (GPU), application Specific Integrated Circuit (ASIC), field Programmable Gate Array (FPGA), or the like.
In another aspect, the present invention provides a system/device for determining a cancer type, the system/device comprising:
the acquisition unit is used for acquiring S100A2 expression data of the sample to be detected;
and a judging unit for comparing the S100A2 expression data with the threshold value and judging the parting result.
Preferably, the system/device may further comprise a detection unit detecting the S100A2 expression level.
Preferably, the detection unit can detect by a real-time quantitative PCR instrument, a high throughput sequencing platform, a detection chip, a chip signal reader, and the like.
Preferably, the chip includes a probe for detecting the S100A2 expression level.
Preferably, the chip comprises a protein chip and/or a gene chip.
Preferably, the system/device further includes an evaluation result transmitting unit that can transmit the typing result of the judging unit to an information communication terminal device that the patient or the medical staff can refer to.
Preferably, the system/device further comprises a user input device, a display device.
Preferably, the user input device is used for inputting personal information of the subject.
Preferably, the display device is used for displaying the conclusion drawn by the computing device.
To provide for interaction with a user, the systems and techniques described here can be implemented on a computer having: display means for displaying information to a user; and a keyboard and pointing device (e.g., a mouse) through which a user can provide input to the computer. Other kinds of devices may also be used to provide for interaction with a user; for example, feedback provided to the user may be any form of sensory feedback (e.g., visual feedback, auditory feedback, or tactile feedback); and input from the user may be received in any form, including acoustic input, speech input, or tactile input.
It should be appreciated that various forms of the flows shown above may be used to reorder, add, or delete steps. For example, the steps recited in the present disclosure may be performed in parallel or sequentially or in a different order, provided that the desired results of the technical solutions of the present disclosure are achieved, and are not limited herein.
In another aspect, the present invention provides a computer readable storage medium having stored thereon a computer program which when executed by a processor performs the following operations:
S100A2 expression data of the sample to be detected are obtained, and the typing result of the sample to be detected is judged by comparing the S100A2 expression data with a threshold value.
In the context of this document, a computer readable storage medium may be any tangible medium that can contain, or store a program for use by or in connection with an instruction execution system, apparatus, or device. The computer readable storage medium may be, for example, an electronic, magnetic, optical, electromagnetic, infrared, or semiconductor system, apparatus, or device, or any combination thereof.
As used herein, the terms "sample," "test sample" may be any biological sample isolated from a subject. For example, the sample may include, but is not limited to, body fluids, whole blood, platelets, serum, plasma, stool, erythrocytes, leukocytes or leukocytes, endothelial cells, tissue, synovial fluid, lymph, ascites, interstitial or extracellular fluid, fluid in the intercellular space, including gingival crevicular fluid, bone marrow, cerebrospinal fluid, saliva, mucus, sputum, semen, sweat, urine, nasal brush fluid, pap smear fluid, or any other body fluid. The body fluid may include saliva, blood or serum.
The sample to be tested according to the invention is preferably a tissue, in particular a biopsy tissue sample or a tissue culture or a cell derived therefrom. The source of tissue may be solid tissue, such as from fresh, frozen and/or preserved organs or tissue samples, biopsy tissue or aspirates.
Specifically, the sample to be tested is collected from a subject; preferably, the subject is a patient with ovarian epithelial cancer (epithelial ovarian carcinoma, EOC), or the subject is a patient with suspected Ovarian Clear Cell Cancer (OCCC), high grade serous ovarian cancer (HGSC).
The term "determining the type of cancer" according to the present invention is understood to mean determining the type of ovarian epithelial cancer (epithelial ovarian carcinoma, EOC), as a result of which the type is Ovarian Clear Cell Carcinoma (OCCC) or high grade serous ovarian carcinoma (HGSC).
The "S100A2 expression data" as used herein refers to the amount of the polynucleotide of S100A2 or the amino acid product or protein of S100A2 in a sample, and may be referred to as "S100A2 expression level" or "S100A2 expression level".
In another aspect, the invention provides the use of a reagent for detecting the amount of S100A2 expression in the preparation of a product for determining the type of cancer.
In particular, the typing is Ovarian Clear Cell Carcinoma (OCCC) or high grade serous ovarian carcinoma (HGSC). Alternatively, the determining of the cancer type refers to determining the type of ovarian epithelial cancer (epithelial ovarian carcinoma, EOC).
Preferably, the expression level includes an mRNA expression level or a protein expression level.
Preferably, the reagent comprises:
a reagent for detecting the mRNA expression level of S100A2 in a sample;
a reagent for detecting the protein expression level of S100A2 in a sample; or (b)
And (3) detecting the number of S100A2 positive expression cells in the sample.
Further, the product comprises a detection kit and a biochip.
Further, the detection kit further comprises one or more substances selected from the group consisting of: a container, instructions for use, positive control, negative control, buffer, adjuvant, or solvent.
Further, the detection kit includes: RT-PCR detection kit, ELISA detection kit, protein chip detection kit, rapid detection kit, DNA chip detection kit, immunohistochemical detection kit, or MRM (multiple reaction monitoring) detection kit.
In another aspect, the invention also provides a method of distinguishing between an Ovarian Clear Cell Carcinoma (OCCC) patient and a high grade serous ovarian carcinoma (HGSC) patient, the method comprising determining that the patient is from an Ovarian Clear Cell Carcinoma (OCCC) patient or a high grade serous ovarian carcinoma (HGSC) patient based on the amount of S100A2 expressed in a sample from the subject.
In another aspect, the invention provides a method for differentiating between ovarian clear cell carcinoma cells and high-grade serous ovarian carcinoma cells, the method comprising determining whether the ovarian clear cell carcinoma cells or the high-grade serous ovarian carcinoma cells are in accordance with the expression level of S100A2 in the test cells.
Drawings
FIG. 1 is a graph showing the results of HE staining and immunohistochemical staining sections of OCCC and HGSC.
FIG. 2 is a Umap diagram of cell visualizations performed by the RunUMAP function.
FIG. 3 is a comparison of S100A2 expression levels in epithelial cell populations (epithelial subpopulations) of 5 OCCC patients and 5 HGSC patients.
FIG. 4 shows the results of RT-PCR and immunoblotting.
Fig. 5 is a representative image in a tissue chip.
Detailed Description
The present invention is further described in terms of the following examples, which are given by way of illustration only, and not by way of limitation, of the present invention, and any person skilled in the art may make any modifications to the equivalent examples using the teachings disclosed above. Any simple modification or equivalent variation of the following embodiments according to the technical substance of the present invention falls within the scope of the present invention.
Example 1 screening for novel signature molecular markers in OCCC and HGSC
All patients received surgical resection in Beijing co-ordination and all patients had no treatment prior to surgery. Patients with mixed cancer, ovarian and uterine double primary cancer were excluded. All patients were diagnosed by 3 experienced pathologists, each according to the 2020 world health organization classification, and were staged (typed) using NCCN ovarian cancer guidelines (version 3.2022). The study was approved by the ethical committee of Beijing co-ordinates, hospital (JS-3553). All patients had informed consent.
The present invention collects tumor biopsies from the above 5 OCCC patients and 5 HGSC patients, detailed clinical information is shown in Table 1, and representative H & E and IHC staining images are shown in FIG. 1.
TABLE 1 clinical pathological characteristics of patients in single cell sequencing
Note that: tumor size is a measure of the longest axis of the primary tumor. The size of bilateral tumors is listed as the size of left tumor/the size of right tumor.
Tumor biopsies of the above patients were subjected to 3'sc RNA-seq, library construction using Chromium Next GEM Single Cell 3'GEM,Library&Gel Bead Kit v3.1 (10 x Genomics, USA) and single cell sequencing using Illumina Nova Seq 6000 (norstanding, beijing, china). After filtering out low quality cells and diploids we integrated all 10 samples into one gene expression matrix for a total of 101,672 cells, with an average of 2000 genes per cell.
Raw sequencing data from the above 10 patients were processed according to the GRCh38 human reference genome, according to chromanum's Cell Ranger pipeline (version 4.0.0). The data was filtered from individual cell counts in all samples using the setup analysis package in R (v4.1.0) and individual setup objects were created. We further pooled all samples and used a typical correlation analysis (CCA) for dimension reduction (dimension) and batch effect removal (batch effect). Standard unit clustering was then performed using the Scale Data function, principal Component Analysis (PCA) dimensions were calculated using the RunPCA function, and unsupervised clustering was performed on the Data using the Find Neighbors and Find Cluster functions (unsupervised clustering analysis).
Cell visualization by RunUMAP function visible cell aggregation into 3 main populations: epithelial (epihelial), immune (Immune) and stroma (Stromal).
Analysis of the Differentially Expressed Genes (DEGs) of the epithelial cell populations (epithelial subpopulations) of the above 5 OCCC patients and 5 HGSC patients showed that S100A2 was significantly lower in OCCC than HGSC (fig. 3).
Example 2, RT-PCR and Western blot to verify differential expression of S100A2
RT-PCR detection: total RNA was extracted using TRIZOL reagent (Thermo Fisher Scientific) and reverse transcribed into cDNA using Prime ScriptTM RT Master Mix (TAKARA Co., japan). Real-Time fluorescent quantitative PCR was performed using Fast SYBR Green Master Mix (Thermo Fisher Scientific) and Quant studio 7Flex Real-Time PCR System (Thermo Fisher Scientific). The gene expression uses GAPDH as an internal reference, and the primers of S100A2 are as follows:
S100A2-F:5′-TGCCAAGAGGGCGACAAGTTCA-3′,
S100A2-R:5′-AAGTCCACCTGCTGGTCACTGT-3′
western blot detection: cells were lysed with RIPA lysate (bejing aoqing biotechnology limited) containing Prot Lystic Protease Inhibitor Cocktail (New cell & Molecular Biotech), BCA Assay Kit (Pierce Biotechnology, USA) to determine protein concentration. Cell lysates were separated by Nu PAGETM 4-12% gel (Thermo Fisher Scientific) and transferred to polyvinylidene difluoride (PVDF) (Millipore, USA) membranes. After blocking the membrane, it is incubated with primary antibody and then with secondary antibody. The bands were visualized by enhanced chemiluminescence according to the manufacturer's instructions (Peirce).
The detection result is consistent with the sc RNA-seq sequencing analysis result, the expression of S100A2 in OCCC is obviously lower than that of HGSC, and the result is shown in FIG. 4.
Example 3 verification of the Distinguishing function of S100A2 in clinical samples
Collection of 128 OCCCs and 81 HGSCs patients constructed 2 tissue chips (TMAs). A representative image is shown in fig. 5. The above patients included patients who underwent surgical excision in Beijing co-ordination hospitals from 1 month 2019 to 5 months 2022 and had sufficient archived tissue for immunohistochemical detection. Finally, 128 OCCC patients and 81 HGSC patients were included. Clinical information is shown in Table 2.
Table 2 clinical features of inclusion queue in validation
Note that: the relapse time is defined as the number of months between the first surgery and the time of relapse, considering only patients who relapse.
Two tissue chips were constructed from formalin-fixed, paraffin-embedded tissue. IHC staining procedure was performed as per standard with DAKO Autostainer Link, the primary antibody of S100A2 being ab109494 (Abcam).
The expression of S100A2 in cytoplasm and cell membrane (with cells at esophagus as positive control and matrix cells as negative control) was detected in immunohistochemical staining, and (0-12) was comprehensively scored according to the intensity and percentage of positive cells. Cases with a composite score of 4 or more were considered positive, and other cases were considered negative.
Table 3 comparison of immunohistochemical results for OCCC and HGSC
Note that: the number is the number (percentage) of patients positive for immunohistochemical staining, a is statistically significant
It was calculated that the Sensitivity (Sensitivity) was 33.3%, the Specificity (Specificity) was 96.9%, PPV (positive predictive value) 87.1.1% and the NPV (negative predictive value) was 69.7% in the discrimination between OCCC and HGSC by S100A 2.
Claims (7)
1. Use of an agent for detecting the amount of S100A2 expressed in the manufacture of a product for determining the type of cancer, said type resulting in ovarian clear cell cancer or high grade serous ovarian cancer.
2. The use according to claim 1, wherein the expression level comprises mRNA expression level or protein expression level.
3. The use of claim 1, the agent comprising:
a reagent for detecting the mRNA expression level of S100A2 in a sample;
a reagent for detecting the protein expression level of S100A2 in a sample; or (b)
And (3) detecting the number of S100A2 positive expression cells in the sample.
4. The use according to claim 1, wherein the product comprises a detection kit or a biochip.
5. The use according to claim 4, wherein the detection kit comprises: RT-PCR detection kit, ELISA detection kit, protein chip detection kit, rapid detection kit, DNA chip detection kit, immunohistochemical detection kit, or MRM detection kit.
6. The use of claim 1, wherein the S100A2 expression level is detected for a sample from a subject, the sample being tissue.
7. The use of claim 6, wherein the tissue comprises a biopsy tissue sample or a tissue culture or cell derived therefrom.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202310697259.5A CN116716404B (en) | 2023-06-13 | 2023-06-13 | Device for distinguishing ovarian clear cell carcinoma from high-grade serous carcinoma based on S100A2 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202310697259.5A CN116716404B (en) | 2023-06-13 | 2023-06-13 | Device for distinguishing ovarian clear cell carcinoma from high-grade serous carcinoma based on S100A2 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN116716404A CN116716404A (en) | 2023-09-08 |
CN116716404B true CN116716404B (en) | 2024-01-30 |
Family
ID=87867465
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202310697259.5A Active CN116716404B (en) | 2023-06-13 | 2023-06-13 | Device for distinguishing ovarian clear cell carcinoma from high-grade serous carcinoma based on S100A2 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN116716404B (en) |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2010132958A1 (en) * | 2009-05-22 | 2010-11-25 | Garvan Institute Of Medical Research | Methods for predicting responsiveness to treatment |
GB201607393D0 (en) * | 2016-04-28 | 2016-06-15 | Isis Innovation | Biomarkers for early diagnosis of ovarian cancer |
CN116129998A (en) * | 2023-01-19 | 2023-05-16 | 中国医学科学院肿瘤医院 | Esophageal squamous cell carcinoma data processing method and system |
-
2023
- 2023-06-13 CN CN202310697259.5A patent/CN116716404B/en active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2010132958A1 (en) * | 2009-05-22 | 2010-11-25 | Garvan Institute Of Medical Research | Methods for predicting responsiveness to treatment |
GB201607393D0 (en) * | 2016-04-28 | 2016-06-15 | Isis Innovation | Biomarkers for early diagnosis of ovarian cancer |
CN116129998A (en) * | 2023-01-19 | 2023-05-16 | 中国医学科学院肿瘤医院 | Esophageal squamous cell carcinoma data processing method and system |
Also Published As
Publication number | Publication date |
---|---|
CN116716404A (en) | 2023-09-08 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Pinzani et al. | Isolation by size of epithelial tumor cells in peripheral blood of patients with breast cancer: correlation with real-time reverse transcriptase–polymerase chain reaction results and feasibility of molecular analysis by laser microdissection | |
Bird–Lieberman et al. | Population-based study reveals new risk-stratification biomarker panel for Barrett's esophagus | |
Kalloger et al. | Calculator for ovarian carcinoma subtype prediction | |
AU2013265267B2 (en) | Process for multi-analyses of rare cells extracted or isolated from biological samples through filtration | |
de Carvalho et al. | Accuracy of microRNAs as markers for the detection of neck lymph node metastases in patients with head and neck squamous cell carcinoma | |
KR101921945B1 (en) | Lung cancer biomarkers and uses thereof | |
US20070065859A1 (en) | Methods and materials for identifying the origin of a carcinoma of unknown primary origin | |
US10180430B2 (en) | Methods for detecting human papillomavirus and providing prognosis for head and neck squamous cell carcinoma | |
CN104024436B (en) | Marker gene for carcinoma of prostate classification | |
CN103733065A (en) | Molecular diagnostic test for cancer | |
KR102412396B1 (en) | Early lung cancer detection by dna methylation phenotyping of sputum-derived cells | |
CN108884494A (en) | The unicellular Genome Atlas of circulating tumor cell is analyzed to characterize disease heterogeneity in metastatic disease | |
Brunner et al. | A shared transcriptional program in early breast neoplasias despite genetic and clinical distinctions | |
CN113215254A (en) | Immune-clinical characteristic combined prediction model for evaluating lung adenocarcinoma prognosis | |
US20220042106A1 (en) | Systems and methods of using cell-free nucleic acids to tailor cancer treatment | |
CN116716404B (en) | Device for distinguishing ovarian clear cell carcinoma from high-grade serous carcinoma based on S100A2 | |
CN108603233A (en) | The unicellular Genome Atlas of circulating tumor cell (CTC) is analyzed to characterize disease heterogeneity in metastatic disease | |
Hamada et al. | Diagnostic usefulness of PCR profiling of the differentially expressed marker genes in thyroid papillary carcinomas | |
EP3636779A1 (en) | Pre-surgical risk stratification based on pde4d7 and dhx9 expression | |
Selaru et al. | An unsupervised approach to identify molecular phenotypic components influencing breast cancer features | |
Dotson et al. | Feasibility of lung cancer RNA acquisition from a single transbronchial or transthoracic needle pass (FASTT trial) | |
CN113759132B (en) | Models, products, and methods for predicting prognosis of endometrial cancer | |
CN115505644A (en) | Kit for predicting chemotherapeutic effect of head and neck squamous cell carcinoma and application thereof | |
CN116855605B (en) | Application of AOC1 as marker for distinguishing ovarian clear cell carcinoma and high-grade serous carcinoma | |
CN111500733B (en) | Molecular marker for early diagnosis of non-small cell lung cancer in peripheral blood mononuclear cells |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |