WO2020184550A1 - Cancer marker and use therefor - Google Patents

Cancer marker and use therefor Download PDF

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WO2020184550A1
WO2020184550A1 PCT/JP2020/010236 JP2020010236W WO2020184550A1 WO 2020184550 A1 WO2020184550 A1 WO 2020184550A1 JP 2020010236 W JP2020010236 W JP 2020010236W WO 2020184550 A1 WO2020184550 A1 WO 2020184550A1
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antibody
cancer
cancer marker
derived
marker
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PCT/JP2020/010236
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French (fr)
Japanese (ja)
Inventor
浩之 竹田
澤崎　達也
吉博 三宅
洋平 宮城
智之 横瀬
年成 山下
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国立大学法人愛媛大学
地方独立行政法人神奈川県立病院機構
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Priority to JP2021505075A priority Critical patent/JP7432578B2/en
Publication of WO2020184550A1 publication Critical patent/WO2020184550A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • 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
    • G01N33/15—Medicinal preparations ; Physical properties thereof, e.g. dissolubility
    • 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
    • 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
    • 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
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • 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
    • 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
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids

Definitions

  • the present invention relates to a cancer marker, a method for testing the risk of developing cancer using the marker, a test kit for cancer, a method for measuring the cancer marker, and a method for screening a cancer therapeutic agent.
  • Non-Patent Documents 1 to 6 Non-Patent Documents 1 to 6).
  • Duffy MJ “Use of Biomarkers in Screening for Cancer.”, Adv Exp Med Biol, 2015, vol. 867, pages 27-39, doi: 10.1007 / 978-94-017-7215-0_3.
  • an object of the present invention is to provide a new cancer marker for testing the risk of developing cancer.
  • the cancer markers of the present invention include anti-HIRIP3 antibody, HIRIP3, anti-FNDC11 antibody, FNDC11, anti-SLC1A3 antibody, SLC1A3, anti-TMEM33 antibody, TMEM33, anti-ABCF1 antibody, ABCF1, anti-CFDP1 antibody, CFDP1, anti-POLR3GL antibody, POLR3GL It comprises at least one selected from the group consisting of anti-CADM1 antibody, CADM1, anti-RNF128 antibody, RNF128, anti-ATP6V1B1 antibody, and ATP6V1B1.
  • the method for testing the risk of developing cancer of the present invention includes a step of measuring the expression level of a cancer marker in a biological sample of a subject.
  • the cancer markers include anti-HIRIP3 antibody, HIRIP3, anti-FNDC11 antibody, FNDC11, anti-SLC1A3 antibody, SLC1A3, anti-TMEM33 antibody, TMEM33, anti-ABCF1 antibody, ABCF1, anti-CFDP1 antibody, CFDP1, anti-POLR3GL antibody, POLR3GL, anti-CAMM1 Includes at least one selected from the group consisting of antibody, CADM1, anti-RNF128 antibody, RNF128, anti-ATP6V1B1 antibody, and ATP6V1B1.
  • the cancer test kit of the present invention contains a reagent for measuring the expression of a cancer marker.
  • the cancer markers include anti-HIRIP3 antibody, HIRIP3, anti-FNDC11 antibody, FNDC11, anti-SLC1A3 antibody, SLC1A3, anti-TMEM33 antibody, TMEM33, anti-ABCF1 antibody, ABCF1, anti-CFDP1 antibody, CFDP1, anti-POLR3GL antibody, POLR3GL, anti-CAMM1 Includes at least one selected from the group consisting of antibody, CADM1, anti-RNF128 antibody, RNF128, anti-ATP6V1B1 antibody, and ATP6V1B1.
  • the method for measuring a cancer marker of the present invention includes a step of contacting a biological sample of a subject with a reagent for measuring the expression of a cancer marker and measuring the expression level of the cancer marker in the biological sample.
  • the cancer markers include anti-HIRIP3 antibody, HIRIP3, anti-FNDC11 antibody, FNDC11, anti-SLC1A3 antibody, SLC1A3, anti-TMEM33 antibody, TMEM33, anti-ABCF1 antibody, ABCF1, anti-CFDP1 antibody, CFDP1, anti-POLR3GL antibody, POLR3GL, anti-CAMM1 Includes at least one selected from the group consisting of antibody, CADM1, anti-RNF128 antibody, RNF128, anti-ATP6V1B1 antibody, and ATP6V1B1.
  • the method for screening a candidate substance for a cancer therapeutic agent of the present invention includes a step of selecting an expression-suppressing substance that suppresses the expression of a cancer marker from a test substance as the therapeutic candidate substance.
  • the cancer markers include anti-HIRIP3 antibody, HIRIP3, anti-FNDC11 antibody, FNDC11, anti-SLC1A3 antibody, SLC1A3, anti-TMEM33 antibody, TMEM33, anti-ABCF1 antibody, ABCF1, anti-CFDP1 antibody, CFDP1, anti-POLR3GL antibody, POLR3GL, anti-CAMM1 Includes at least one selected from the group consisting of antibody, CADM1, anti-RNF128 antibody, RNF128, anti-ATP6V1B1 antibody, and ATP6V1B1.
  • the present inventor has found that autoantibodies against HIRIP3, FNDC11, SLC1A3, TMEM33, ABCF1, CFDP1, POLR3GL, CADM1, RNF128, and ATP6V1B1 in vivo correlate with the onset of cancer. It came to establish the invention.
  • the marker of the present invention By measuring the expression level of the marker of the present invention, the risk of developing cancer in a subject can be tested.
  • a candidate substance for the treatment of cancer can be obtained by screening using the marker of the present invention. Therefore, the present invention is extremely useful in the clinical and biochemical fields.
  • FIG. 1 is a graph showing the results of the Alpha Screen of Example 1.
  • FIG. 2 is a graph showing the results of the Alpha Screen of Example 2.
  • FIG. 3 is a graph showing the results of the Alpha Screen of Example 3.
  • FIG. 4 is a photograph showing the results of immunostaining of Example 4.
  • FIG. 5 is a graph showing the results of immunostaining of Example 5.
  • FIG. 6 is a photograph showing the results of immunostaining of Example 6.
  • FIG. 7 is a graph showing the results of the Alpha Screen of Example 7.
  • FIG. 8 is a graph showing the results of the Alpha Screen of Example 8.
  • FIG. 9 is a graph showing the results of the Alpha Screen of Example 9.
  • the cancer markers of the present invention include anti-HIRI P3 antibody, HIRIP3, anti-FNDC11 antibody, FNDC11, anti-SLC1A3 antibody, SLC1A3, anti-TMEM33 antibody, TMEM33, anti-ABCF1 antibody, ABCF1, anti-CFDP1 antibody, CFDP1, anti. It comprises at least one selected from the group consisting of POLR3GL antibody, POLR3GL, anti-CADM1 antibody, CADM1, anti-RNF128 antibody, RNF128, anti-ATP6V1B1 antibody, and ATP6V1B1.
  • the risk of developing cancer in the subject can be tested by measuring the expression level of the cancer marker in the biological sample of the subject.
  • anti-HIRIP3 antibody, anti-FNDC11 antibody, anti-SLC1A3 antibody, anti-TMEM33 antibody, anti-ABCF1 antibody, anti-CFDP1 antibody, anti-POLR3GL antibody, anti-CADM1 antibody, anti-RNF128 antibody, and anti-ATP6V1B1 antibody are used as antibodies of the present invention. Also called. Further, HIRIP3, FNDC11, SLC1A3, TMEM33, ABCF1, CFDP1, POLR3GL, CADM1, RNF128, and ATP6V1B1 are also referred to as antigen proteins of the present invention.
  • the origin of the antibody and antigen protein of the present invention is not particularly limited and can be appropriately set depending on the type of subject, for example.
  • the origin includes, for example, humans, non-human animals other than humans, and examples of the non-human animals include mammals such as mice, rats, dogs, monkeys, rabbits, sheep, and horses.
  • the antibody and antigen protein of the present invention are preferably derived from humans, for example.
  • information registered in an existing database can be referred to.
  • the antibody of the present invention may bind to the corresponding antigen protein, or may bind to a peptide consisting of a partial sequence thereof, that is, a peptide fragment of the corresponding antigen protein.
  • Human-derived HIRIP3 can be used as a cDNA, for example, as a protein in the underlined region (492-2161) in the following nucleotide sequence (SEQ ID NO: 1) registered in NCBI Accession No. NM_003609.4.
  • SEQ ID NO: 1 the amino acid sequence registered under NCBI accession number NP_003600.2
  • the base sequence of SEQ ID NO: 1 is a sequence encoding the amino acid sequence of SEQ ID NO: 2.
  • Human-derived HIRIP3 protein (SEQ ID NO: 2) MAREKEMQEFTRSFFRGRPDLSTLTHSIVRRRYLAHSGRSHLEPEEKQALKRLVEEELLKMQVDEAASREDKLDLTKKGKRPPTPCSDPERKRFRFNSESESGSEASSPDYFGPPAKNGVAAEVSPAKEENPRRASKAVEESSDEERQRDLPAQRGEESSEEEEKGYKGKTRKKPVVKKQAPGKASVSRKQAREESEESEAEPVQRTAKKVEGNKGTKSLKESEQESEEEILAQKKEQREEEVEEEEKEEDEEKGDWKPRTRSNGRRKSAREERSCKQKSQAKRLLGDSDSEEEQKEAASSGDDSGRDREPPVQRKSEDRTQLKGGKRLSGSSEDEEDSGKGEPTAKGSRKMARLGSTSGEESDLEREVSDSEAGGGPQGERKNRSSKKSSRKGRTRSSSSSSDGSPEAKGGKAGSGRRGEDHPAVMRLKRYIRACGAHRNYKKLLGSCC
  • Human-derived FNDC11 is used as a cDNA, for example, as a protein in the underlined region (93-1049) in the following nucleotide sequence (SEQ ID NO: 3) registered in NCBI Accession No. NM_024059.3 (including stop codons).
  • SEQ ID NO: 3 registered in NCBI Accession No. NM_024059.3 (including stop codons).
  • amino acid sequence SEQ ID NO: 4 registered under NCBI accession number NP_076964.1 can be mentioned.
  • the base sequence of SEQ ID NO: 3 is a sequence encoding the amino acid sequence of SEQ ID NO: 4.
  • Human-derived FNDC11 protein (SEQ ID NO: 4) MSTHVAGLGLDKMKLGNPQSFLDQEEADDQQLLEPEAWKTYTERRNALREFLTSDLSPHLLKRHHARMQLLRKCSYYIEVLPKHLALGDQNPLVLPSALFQLIDPWKFQRMKKVGTAQTKIQLLLLGDLLEQLDHGRAELDALLRSPDPRPFLADWALVERRLADVSAVMDSFLTMMVPGRLHVKHRLVSDVSATKIPHIWLMLSTKMPVVFDRKASAAHQDWARLRWFVTIQPATSEQYELRFRLLDPRTQQECAQCGVIPVAACTFDVRNLLPNRSYKFTIKRAETSTLVYEPWRDSLTLHTKPEPLEGPALSHSV
  • Human-derived SLC1A3 is used as a cDNA, for example, as a protein in the underlined portion (226-1854) region (including stop codon) in the following nucleotide sequence (SEQ ID NO: 5) registered at NCBI Accession No. NM_004172.5.
  • SEQ ID NO: 5 the following amino acid sequence registered under NCBI accession number NP_004163.3.
  • the base sequence of SEQ ID NO: 5 is a sequence encoding the amino acid sequence of SEQ ID NO: 6.
  • Human-derived SLC1A3 cDNA (SEQ ID NO: 5) 5'-AGAGCACATGCACACTGTCAGGGCTAGCCTGCCTGCTTACGCGCGCTGCGGATTGTTGCTCCGTTGTACCTGCTGGGGAATTCACCTCGTTACTGCTTGATATCTTCCACCCCTTACAAAAATCAGAAAAGTTGTGTTTTCTAATACCAAAGGAGGTTTGGCTTTCTAATACCAAAGGAGGTTTGGCTTTCTGGGTAGA.
  • Human-derived SLC1A3 protein (SEQ ID NO: 6) MTKSNGEEPKMGGRMERFQQGVRKRTLLAKKKVQNITKEDVKSYLFRNAFVLLTVTAVIVGTILGFTLRPYRMSYREVKYFSFPGELLMRMLQMLVLPLIISSLVTGMAALDSKASGKMGMRAVVYYMTTTIIAVVIGIIIVIIIHPGKGTKENMHREGKIVRVTAADAFLDLIRNMFPPNLVEACFKQFKTNYEKRSFKVPIQANETLVGAVINNVSEAMETLTRITEELVPVPGSVNGVNALGLVVFSMCFGFVIGNMKEQGQALREFFDSLNEAIMRLVAVIMWYAPVGILFLIAGKIVEMEDMGVIGGQLAMYTVTVIVGLLIHAVIVLPLLYFLVTRKNPWVFIGGLLQALITALGTSSSSATLPITFKCLEENNGVDKRVTRFVLPVGATINMDGTALYEALAAIFIAQVNNFEL
  • Human-derived TMEM33 can be used as a cDNA, for example, as a protein in the underlined region (57-800th) region (including stop codon) in the following nucleotide sequence (SEQ ID NO: 7) registered at NCBI Accession No. NM_018126.3.
  • SEQ ID NO: 7 registered at NCBI Accession No. NM_018126.3.
  • amino acid sequence SEQ ID NO: 8 registered under NCBI accession number NP_060596.2 can be mentioned.
  • the nucleotide sequence of SEQ ID NO: 7 is a sequence encoding the amino acid sequence of SEQ ID NO: 8.
  • Human-derived TMEM33 protein (SEQ ID NO: 8) MADTTPNGPQGAGAVQFMMTNKLDTAMWLSRLFTVYCSALFVLPLLGLHEAASFYQRALLANALTSALRLHQRLPHFQLSRAFLAQALLEDSCHYLLYSLIFVNSYPVTMSIFPVLLFSLLHAATYTKKVLDARGSNSLPLLRSVLDKLSANQNILKVLDARGSNSLPLLRSVLDKLSANQNILKVLDARGSNSLPLLRSVLDKLSANQNILKVLDARGSNSLPLLRSVLDKLSANQNILKVLDARGSNSLPLLRSVLDKLSANQNILKVLDARGSNSLPLLRSVLDKLSANQNILKVLDARGSNSLPLLRSVLDKLSANQNILKVLDARGSNSLPLLRSVLDKLSANQNILKVLDARGSNSLPLLRSVLDKLSANQNILKVLDARGSNSLPLLRSVLDKLSANQNILKVLDARGSNSL
  • Human-derived ABCF1 is used as a cDNA, for example, as a protein in the underlined region (47-2584th) in the following nucleotide sequence (SEQ ID NO: 9) registered in NCBI accession number NM_001025091.2 (including stop codon).
  • SEQ ID NO: 9 the following amino acid sequence registered under NCBI accession number NP_001020262.1 can be mentioned.
  • the nucleotide sequence of SEQ ID NO: 9 is a sequence encoding the amino acid sequence of SEQ ID NO: 10.
  • Human-derived CFDP1 can be used as a cDNA, for example, as a protein in the underlined region (152-1051) in the following nucleotide sequence (SEQ ID NO: 11) registered in NCBI Accession No. NM_006324.3 (including stop codons).
  • SEQ ID NO: 11 the following amino acid sequence registered under NCBI accession number NP_006315.1 can be mentioned.
  • the nucleotide sequence of SEQ ID NO: 11 is a sequence encoding the amino acid sequence of SEQ ID NO: 12.
  • Human-derived CFDP1 protein (SEQ ID NO: 12) MEEFDSEDFSTSEEDEDYVPSGGEYSEDDVNELVKEDEVDGEEQTQKTQGKKRKAQSIPARKRRQGGLSLEEEEEEDANSESEGSSSEEEDDAAEQEKGIGSEDARKKKEDELWASFLNDVGPKSKVPPSTQVKKGEETEETSSSKLLVKAEELEKPKETEKVKITKVFDFAGEEVRVTKEVDATSKEAKSFFKQNEKEKPQANVPSALPSLPAGSGLKRSSGMSSLLGKIGAKKQKMSTLEKSKLDWESFKEEEGIGEELAIHNRGKEGYIERKAFLDRVDHRQFEIERDLRLSKMKP
  • Human-derived POLR3GL can be used as a cDNA, for example, as a protein in the underlined region (121-777th) region (including stop codon) in the following nucleotide sequence (SEQ ID NO: 13) registered at NCBI Accession No. NM_032305.3.
  • SEQ ID NO: 13 the underlined region (121-777th) region (including stop codon) in the following nucleotide sequence (SEQ ID NO: 13) registered at NCBI Accession No. NM_032305.3.
  • amino acid sequence SEQ ID NO: 14
  • the nucleotide sequence of SEQ ID NO: 13 is a sequence encoding the amino acid sequence of SEQ ID NO: 14.
  • Human-derived POLR3GL protein (SEQ ID NO: 14) MASRGGGRGRGRGQLTFNVEAVGIGKGDALPPPTLQPSPLFPPLEFRPVPLPSGEEGEYVLALKQELRGAMRQLPYFIRPAVPKRDVERYSDKYQMSGPIDNAIDWNPDWRRLPRELKIRVRKLQKERITILLPKRPPKTTEDKEETIQKLETLEKKEEEVTSEEDEE
  • Human-derived CADM1 can be used as a cDNA, for example, as a protein in the underlined region (130-1458th) of the following nucleotide sequence (SEQ ID NO: 15) registered at NCBI Accession No. NM_014333.3 (including stop codons).
  • SEQ ID NO: 15 the following amino acid sequence registered under NCBI accession number NP_055148.3 can be mentioned.
  • the nucleotide sequence of SEQ ID NO: 15 is a sequence encoding the amino acid sequence of SEQ ID NO: 16.
  • Human-derived RNF128 can be used as a cDNA, for example, as a protein in the underlined region (214-1500) (including stop codons) in the following nucleotide sequence (SEQ ID NO: 17) registered at NCBI Accession No. NM_194463.2.
  • SEQ ID NO: 17 the underlined region registered at NCBI Accession No. NM_194463.2.
  • amino acid sequence SEQ ID NO: 18 registered under NCBI accession number NP_919445.1 can be mentioned.
  • the nucleotide sequence of SEQ ID NO: 17 is a sequence encoding the amino acid sequence of SEQ ID NO: 18.
  • Human-derived ATP6V1B1 is used as a cDNA, for example, as a protein in the underlined region (56-1597) (including stop codons) in the following nucleotide sequence (SEQ ID NO: 19) registered at NCBI Accession No. NM_001692.4.
  • SEQ ID NO: 19 the following amino acid sequence registered under NCBI accession number NP_001683.2.
  • the nucleotide sequence of SEQ ID NO: 19 is a sequence encoding the amino acid sequence of SEQ ID NO: 20.
  • Human-derived ATP6V1B1 protein (SEQ ID NO: 20) MAMEIDSRPGGLPGSSCNLGAAREHMQAVTRNYITHPRVTYRTVCSVNGPLVVLDRVKFAQYAEIVHFTLPDGTQRSGQVLEVAGTKAIVQVFEGTSGIDARKTTCEFTGDILRTPVSEDMLGRVFNGSGKPIDKGPVVMAEDFLDINGQPINPHSRIYPEEMIQTGISPIDVMNSIARGQKIPIFSAAGLPHNEIAAQICRQAGLVKKSKAVLDYHDDNFAIVFAAMGVNMETARFFKSDFEQNGTMGNVCLFLNLANDPTIERIITPRLALTTAEFLAYQCEKHVLVILTDMSSYAEALREVSAAREEVPGRRGFPGYMYTDLATIYERAGRVEGRGGSITQIPILTMPNDDITHPIPDLTGFITEGQIYVDRQLHNRQIYPPINVLPSLSRLMKSAIGEGMTRKDHGDVSNQLYAC
  • the cancer marker of the present invention is selected from the group consisting of anti-human-derived HIRIP3 antibody, anti-human-derived FNDC11 antibody, anti-human-derived SLC1A3 antibody, and anti-human-derived TMEM33 antibody, for example, because of its higher accuracy as a marker. It is preferable to contain at least one antibody, and more preferably to contain an anti-human-derived HIRIP3 antibody.
  • the cancer marker of the present invention may be used alone or in combination of two or more.
  • the combination of cancer markers of the present invention is not particularly limited and can be any combination of cancer markers.
  • the combination of cancer markers of the present invention includes an anti-human-derived HIRIP3 antibody, an anti-human-derived FNDC11 antibody, an anti-human-derived SLC1A3 antibody, and an anti-human-derived TMEM33 antibody because of its higher accuracy as a marker. Is preferable.
  • the antibody and antigen protein of the present invention can be used as cancer markers, and specifically, for example, breast cancer, ovarian cancer, pancreatic cancer, liver cancer, bile duct cancer, colon cancer, colon cancer, and the like. It can be used as a cancer marker for rectal cancer, gastric cancer, oral cancer, and lung cancer, and is preferably used as a breast cancer marker because it can be detected more accurately.
  • Breast cancer is preferable as the cancer.
  • the breast cancer is not particularly limited, and examples thereof include ductal carcinoma and lobular cancer. According to the cancer marker of the present invention, for example, either a primary tumor or a metastatic cancer can be tested.
  • the marker of the present invention may be, for example, the antibody and antigen protein of the present invention, or mRNA transcribed from the gene of the antibody and antigen protein of the present invention.
  • the method for testing the risk of developing cancer of the present invention includes a step (measurement step) of measuring the expression level of a cancer marker in a biological sample of a subject, and the cancer marker is the above-mentioned. It is characterized by containing the cancer marker of the present invention.
  • the present invention is characterized in that the expression level of the antibody and antigen protein of the present invention is measured as a cancer marker, and other steps and conditions are not particularly limited.
  • the test method of the present invention can be referred to the description of the cancer marker of the present invention.
  • the possibility of developing cancer, the presence or absence of the onset of cancer (whether or not it has become cancerous), the degree of cancer progression, the state of prognosis, and the like can be evaluated.
  • the target cancers are, for example, breast cancer, ovarian cancer, pancreatic cancer, liver cancer, bile duct cancer, colon cancer, colon cancer, rectal cancer, stomach cancer, oral cancer, etc.
  • Breast cancer is preferable because lung cancer and the like can be detected more accurately.
  • either a primary tumor or a metastatic cancer can be tested.
  • the subject includes, for example, humans, non-human animals other than humans, and the non-human animals include, for example, mice, rats, dogs, monkeys, and rabbits, as described above. , Sheep, horses and other mammals.
  • the type of the biological sample is not particularly limited, and examples thereof include body fluids, body fluid-derived cells, organelles, tissues, and cells separated from the living body.
  • the body fluid include blood samples, and specific examples thereof include whole blood, serum, and plasma.
  • the body fluid-derived cells include blood-derived cells, and specific examples thereof include blood cell cells such as blood cells, white blood cells, and lymphocytes.
  • the biological sample can be appropriately determined, for example, according to the type of cancer to be tested.
  • the biological sample is, for example, derived from an organ in which the cancer under test can develop.
  • the organs are, for example, breast, ovary, pancreas, liver, bile duct, large intestine, colon, rectum, stomach, oral cells, lung and the like.
  • the cancer is breast cancer
  • breast-derived tissues or cells such as mammary glands and ducts are preferable.
  • cancer can be tested by the expression level of the cancer marker of the present invention in blood. Therefore, for example, the biological sample is preferably whole blood, serum, or plasma, and more preferably serum or plasma, because the burden on the patient or doctor can be reduced.
  • the measurement of the expression level of the cancer marker in the measurement step may be, for example, analysis of the presence or absence of the cancer marker of the present invention in the biological sample (qualitative analysis), or analysis of the amount of the cancer marker (quantitative analysis). It may be.
  • the cancer marker to be measured in the measurement step is the cancer marker of the present invention, and specifically, anti-HIRIP3 antibody, HIRIP3, anti-FNDC11 antibody, FNDC11, anti-SLC1A3 antibody, SLC1A3, anti-TMEM33 antibody, TMEM33.
  • Anti-ABCF1 antibody, ABCF1, anti-CFDP1 antibody, CFDP1, anti-POLR3GL antibody, POLR3GL, anti-CADM1 antibody, CADM1, anti-RNF128 antibody, RNF128, anti-ATP6V1B1 antibody, and ATP6V1B1 at least one selected from the group.
  • the cancer marker is selected from the group consisting of an anti-human-derived HIRIP3 antibody, an anti-human-derived FNDC11 antibody, an anti-human-derived SLC1A3 antibody, and an anti-human-derived TMEM33 antibody because of its higher accuracy as a marker, for example. It preferably contains one antibody, more preferably an anti-human derived HIRIP3 antibody.
  • the combination of cancer markers of the present invention is not particularly limited and can be any combination of cancer markers.
  • the combination of cancer markers of the present invention includes an anti-human-derived HIRIP3 antibody, an anti-human-derived FNDC11 antibody, an anti-human-derived SLC1A3 antibody, and an anti-human-derived TMEM33 antibody because of its higher accuracy as a marker. Is preferable.
  • the expression of the cancer marker of the present invention to be measured may be the expression of the antibody and / or antigen protein of the present invention, or the expression of mRNA of these genes.
  • the antibody and / or the antigen protein may be measured, the mRNA of these genes may be measured, or both may be measured with respect to the biological sample.
  • the method for measuring various cancer markers is not particularly limited, and a known method can be adopted.
  • the method for measuring mRNA expression includes, for example, a gene amplification method using a reverse transcription reaction such as a reverse transcription (RT) -PCR method.
  • it is a method of synthesizing cDNA from mRNA by a reverse transcription reaction and amplifying the gene using the cDNA as a template.
  • the method for measuring protein expression include an immunoantibody method such as chemiluminescent enzyme immunoassay (CLEIA), an ELISA method, flow cytometry, and Western blotting.
  • CLIA chemiluminescent enzyme immunoassay
  • ELISA ELISA
  • the test method of the present invention further comprises comparing the expression level of the cancer marker of the present invention in the biological sample of the subject (hereinafter, also referred to as “test biological sample”) with a reference value. It may include a step (testing step) of testing the examiner's risk of developing cancer.
  • the reference value is not particularly limited, and examples thereof include the expression level of the cancer marker of the present invention in healthy subjects, cancer patients, and cancer patients at each stage of progression. In the case of evaluation of prognosis, the reference value may be, for example, the expression level of the cancer marker of the present invention after treatment (for example, immediately after treatment) of the same subject.
  • the reference value can be obtained, for example, by using a biological sample (hereinafter, also referred to as "reference biological sample") isolated from a healthy person and / or a cancer patient as described above. Further, in the case of evaluation of prognosis, for example, a reference biological sample isolated after treatment from the same subject may be used. The reference value may be measured at the same time as the test biological sample of the subject, or may be measured in advance. In the latter case, for example, it is not necessary to obtain a reference value every time the test biological sample of the subject is measured, which is preferable. It is preferable that the test biological sample of the subject and the reference biological sample are collected under the same conditions, and the cancer marker of the present invention is measured under the same conditions.
  • the method for evaluating the risk of developing cancer in a subject is not particularly limited, and can be appropriately determined depending on the type of the reference value.
  • the expression level of the cancer marker of the present invention in the test biological sample of the subject is significantly higher than the expression level of the cancer marker of the present invention in the reference biological sample of the healthy subject, the above.
  • the expression level of the cancer marker of the present invention in the reference biological sample of the cancer patient when there is no significant difference) and / or, the expression level of the cancer marker of the present invention in the reference biological sample of the cancer patient If it is significantly higher than, the subject can be assessed as at risk or at high risk of developing cancer.
  • the expression level of the cancer marker of the present invention in the test biological sample of the subject is the same as the expression level of the cancer marker of the present invention in the reference biological sample of the healthy subject (when there is no significant difference).
  • the expression level of the cancer marker of the present invention in the test biological sample of the subject is measured by the expression level of the cancer marker of the present invention in the reference biological sample of the cancer patient for each stage of progression.
  • the degree of cancer progression can be evaluated by comparing with. Specifically, when the test biological sample of the test subject has an expression level similar to that of the reference biological sample of any progression stage (when there is no significant difference), the test subject It can be evaluated that there is a possibility of the progress stage.
  • the evaluation may be made in the same manner as described above, or as a reference value, the cancer marker of the present invention in the reference biological sample after treatment of the same subject. It can also be evaluated using the expression level.
  • the expression level of the cancer marker of the present invention in the test biological sample of the subject is significantly higher than the reference value, the subject is at risk of recurrence or deterioration after the treatment. It can be evaluated as having sex.
  • the expression level of the cancer marker of the present invention in the test biological sample of the subject is the same as the reference value (when there is no significant difference) and / or when it is significantly lower than the reference value. The subject can be evaluated as having no risk of recurrence or a low risk of recurrence after the treatment.
  • a biological sample of the same subject may be collected over time and the expression level of the cancer marker of the present invention in the biological sample may be compared. This makes it possible to determine, for example, that if the expression level increases over time, the possibility of morbidity increases, and if the expression level decreases over time, the possibility of morbidity decreases or It is possible to judge that it has healed.
  • test method of the present invention was evaluated, for example, in the test process, a subject who was evaluated to have a risk of developing cancer or a high risk of developing cancer, and a subject who was evaluated to have a risk of recurrence or exacerbation after treatment.
  • a step (administration step) of administering a therapeutic agent for cancer to the subject may be further included.
  • the test method of the present invention can also be said to be a cancer test and treatment method.
  • the cancer therapeutic agent is not particularly limited and can be appropriately determined according to the type of cancer.
  • the breast cancer therapeutic agent is, for example, a molecular target drug such as an anti-HER2 antibody, an anti-VEGF antibody, an anti-RANKL antibody, a topoisomerase inhibitor, a microtubule agent, an alkylating agent, a metabolic antagonist, Examples include platinum complexes and hormonal agents.
  • the administration conditions (administration target, dose, administration form, administration method, etc.) of the cancer therapeutic agent are not particularly limited and can be appropriately determined according to the type of the cancer.
  • the cancer test kit of the present invention contains a reagent for measuring the expression of a cancer marker, and the cancer marker contains the cancer marker of the present invention.
  • the test method for the risk of developing cancer of the present invention can be easily performed.
  • the test kit of the present invention is characterized in that the risk of developing cancer is tested based on the expression of the cancer marker of the present invention, and other configurations and conditions are not particularly limited.
  • the test kit of the present invention only needs to be able to measure the expression of the cancer marker of the present invention, and can be used, for example, in the test method of the present invention.
  • the test kit of the present invention can be referred to the description of the cancer marker and the test method of the present invention.
  • the type of the expression measuring reagent is not particularly limited, and can be appropriately set according to, for example, the type of the cancer marker of the present invention.
  • the expression measuring reagent may be, for example, the expression measuring reagent for the antibody and / or the antigen protein of the present invention, or may be the expression measuring reagent for the mRNA of these genes.
  • the test kit of the present invention may contain, for example, only the reagent for measuring the expression of the cancer marker.
  • the cancer marker to be measured by the expression measuring reagent is the cancer marker of the present invention, and specifically, anti-HIRIP3 antibody, HIRIP3, anti-FNDC11 antibody, FNDC11, anti-SLC1A3 antibody, SLC1A3.
  • the cancer marker is selected from the group consisting of an anti-human-derived HIRIP3 antibody, an anti-human-derived FNDC11 antibody, an anti-human-derived SLC1A3 antibody, and an anti-human-derived TMEM33 antibody because of its higher accuracy as a marker, for example. It preferably contains one antibody, more preferably an anti-human derived HIRIP3 antibody.
  • the cancer marker to be measured by the expression measurement reagent may be one type or two or more types.
  • the combination of the cancer markers is not particularly limited and can be any combination of cancer markers.
  • the combination of the cancer markers may include an anti-human-derived HIRIP3 antibody, an anti-human-derived FNDC11 antibody, an anti-human-derived SLC1A3 antibody, and an anti-human-derived TMEM33 antibody because the combination of the cancer markers has higher accuracy as a marker. preferable.
  • the type of the expression measuring reagent for the cancer marker can be appropriately set according to the type of the cancer marker.
  • the cancer markers are the antibodies of the present invention (anti-HIRI P3 antibody, anti-FNDC11 antibody, anti-SLC1A3 antibody, anti-TMEM33 antibody, anti-ABCF1 antibody, anti-CFDP1 antibody, anti-POLR3GL antibody, anti-CADM1 antibody, anti-RNF128 antibody, and /
  • the expression measuring reagent is an antigen protein to which the antibody of the present invention can bind or a peptide consisting of a partial sequence thereof (an antigen corresponding to the cancer marker) and the antibody of the present invention. It may contain a detection reagent capable of detecting.
  • the detection reagent is, for example, an enzyme such as alkaline phosphatase (ALP) or luciferase; a fluorescent substance such as particles or a fluorescent protein; a dye such as a pigment substance; a luminescence, depending on the type of the measurement method. It may be labeled with a substance; an electron donor; a color-developing substrate of an enzyme; a hapten such as DNP (dinitrophenol) or TNP (trinitrophenol), or a vitamin such as biotin;
  • the particles include metal particles such as gold and silver, latex particles such as colored latex particles, and magnetic particles.
  • the magnetic particles include solidified magnetic particles on which a protein is immobilized.
  • the detection reagent may be used in combination with, for example, an enzyme substrate, a reducing agent such as ferrous iron (Fe 2+ ), or the like, depending on the type of the detection method.
  • the substrate of the enzyme is not particularly limited and can be appropriately set according to the enzyme.
  • the substrate of the enzyme includes, for example, CDP-Star (registered trademark), NBT and the like.
  • the detection reagent for detecting the antibody of the present invention may be, for example, an antibody that recognizes the antibody of the present invention.
  • the detection reagent is an antibody, for example, only the primary antibody that binds to the antibody of the present invention may be used, or the primary antibody that binds to the antibody of the present invention and the secondary antibody that binds to the primary antibody ( It may be used in combination with a binding detection reagent).
  • the test kit of the present invention comprises, for example, the antibody of the present invention, the antigen corresponding to the cancer marker, and the primary antibody by detecting the binding of the primary antibody to the antibody of the present invention. Complex can be detected.
  • the test kit of the present invention can detect the binding of the secondary antibody to the primary antibody bound to the antibody of the present invention, for example, to detect the antibody of the present invention and the antigen corresponding to the cancer marker. And the complex of the primary antibody and the secondary antibody can be detected.
  • the detection of the binding can be carried out, for example, by detecting the label of the antibody.
  • the primary antibody is preferably, for example, a labeled labeled antibody.
  • the secondary antibody is preferably, for example, a labeled labeled antibody.
  • the antigen protein corresponding to the cancer marker or a peptide consisting of a partial sequence thereof may be used in a free state or in a carrier-supported state (immobilized state).
  • the antigen comprises, for example, the carrier as the other component.
  • the carrier is not particularly limited, and examples thereof include plates such as well plates, beads, porous bodies, porous membranes, and membranes such as filters.
  • the immobilization may be direct immobilization or indirect immobilization.
  • the test kit of the present invention (hereinafter, also referred to as “first kit”) is, for example, an antigen protein or a portion thereof corresponding to a cancer marker labeled with a first label and a second label.
  • a first reagent containing a sequence, a second reagent in which an antibody capable of binding to the first label is immobilized on a carrier, and an antibody capable of binding to the antibody of the present invention (the primary antibody) are third.
  • the first label is preferably a hapten such as DNP or TNP, and more preferably DNP.
  • the second label is preferably biotin.
  • the third label is preferably ALP.
  • the carrier in the second reagent is preferably a magnetic carrier.
  • the fourth reagent preferably comprises a labeling substance labeled with the first label, and more preferably contains a DNP-labeled lysine.
  • the binding agent capable of binding to the second label is preferably streptavidin.
  • the carrier in the fifth reagent is preferably a magnetic carrier.
  • the substrate in the sixth reagent is preferably a substrate for ALP.
  • the carrier in the second reagent and the fifth reagent is a magnetic carrier.
  • the following description is an example of the antibody detection method of the present invention using the first kit, and the usage of the first kit is not limited to the following description.
  • the biological sample of the subject is brought into contact with the first reagent, the second reagent, and the third reagent, and the antibody of the present invention derived from the biological sample of the subject and the second reagent.
  • a complex (first complex) of the first reagent, the second reagent, and the third reagent is formed (first complex forming step).
  • the antibody in the first reagent and the antibody in the third reagent bind to the antibody of the present invention, and further, with respect to the first label of the antibody in the first reagent.
  • the antibody of the second reagent binds.
  • the first complex can be formed in the first complex forming step.
  • the solid fraction containing the first complex and the other liquid fractions are solid-liquid separated, and the liquid fraction is removed (First solid-liquid separation step).
  • the solid fraction may be washed with, for example, a washing liquid.
  • the solid fraction is brought into contact with the fourth reagent, and from the first complex, the antibody of the present invention derived from the biological sample of the subject, the first reagent, and the first reagent.
  • the complex (second complex) with the reagent of 3 is released (free step).
  • the second complex is produced by competing the first label in the first reagent and the first label in the fourth reagent with respect to the binding site of the antibody in the second reagent. Occurs.
  • the number of molecules of the first label added in the fourth reagent is preferably larger than the number of molecules of the first label in the first reagent, and is preferably an excess amount. More preferred.
  • the liquid fraction containing the second complex and the other solid fractions are solid-liquid separated, and the liquid fraction is recovered ( Second solid-liquid separation step). Further, the liquid fraction is brought into contact with the fifth reagent, and the antibody of the present invention derived from the biological sample of the subject, the first reagent, the third reagent, and the fifth reagent are used. A complex (third complex) with the reagent is formed (second complex forming step). The third complex can be formed by binding the binding substance in the fifth reagent to the second label in the second complex.
  • the solid fraction containing the third complex and the other liquid fractions are solid-liquid separated, and the liquid fraction is removed (the first).
  • the solid fraction may be washed with, for example, a washing liquid.
  • the solid fraction is brought into contact with the sixth reagent, the third label in the third complex is reacted with the substrate, and the obtained signal is detected (detection step). Then, based on the signal, the presence or absence or amount of the antibody of the present invention is detected.
  • the expression measuring reagent is the antigen.
  • a substance that binds to a protein and a detection reagent that detects the binding between the antigen protein and the binding substance may be included.
  • the substance that binds to the cancer marker is not particularly limited as long as it is a substance that binds to the cancer marker, and examples thereof include antibodies and aptamers that recognize the cancer marker.
  • the antibody or aptamer that recognizes the cancer marker may be, for example, labeled. The above-mentioned description can be used for the labeling.
  • the detection reagent is an antibody
  • the primary antibody that binds to the antigen protein may be used, or the primary antibody that binds to the antigen protein and the secondary antibody that binds to the primary antibody (binding detection reagent). May be used in combination with.
  • the test kit can detect a complex of the antigen protein of the present invention and the primary antibody, for example, by detecting the binding of the primary antibody to the antigen protein.
  • the test kit comprises a complex of the antigen protein, the primary antibody, and the secondary antibody, for example, by detecting the binding of the secondary antibody to the primary antibody bound to the antigen protein. Can be detected.
  • the detection of the binding can be carried out, for example, by detecting the label of the antibody.
  • the primary antibody is preferably, for example, a labeled labeled antibody.
  • the secondary antibody is preferably, for example, a labeled labeled antibody.
  • the expression measuring reagent includes a reverse transcription reagent of the mRNA and an amplification reagent of the cDNA reverse transcribed from the mRNA.
  • it may contain a sequence reagent for decoding the base sequence of the mRNA.
  • the expression measuring reagent includes, for example, a primer.
  • the primer can be appropriately designed based on, for example, the gene sequence of the cancer marker of the present invention.
  • the test kit of the present invention contains, for example, an antibody capable of binding to the antigen protein of the present invention labeled with the first label and the second label.
  • a first reagent containing, a second reagent in which an antibody capable of binding to the first label is immobilized on a carrier, and an antibody capable of binding to the antigen protein of the present invention (the primary antibody) are labeled as a third.
  • the first label is preferably a hapten such as DNP or TNP, and more preferably DNP.
  • the second label is preferably biotin.
  • the third label is preferably ALP.
  • the carrier in the second reagent is preferably a magnetic carrier.
  • the fourth reagent preferably comprises a labeling substance labeled with the first label, and more preferably contains a DNP-labeled lysine.
  • the binding agent capable of binding to the second label is preferably streptavidin.
  • the carrier in the fifth reagent is preferably a magnetic carrier.
  • the substrate in the sixth reagent is preferably a substrate for ALP.
  • the second kit can be used, for example, in the same manner as the first kit.
  • the test kit of the present invention may further include, for example, other components.
  • the component include the carrier, the substrate of the enzyme, a buffer solution, a washing solution, reagents such as a release agent between magnetic particles and an antibody, and instructions for use.
  • the liberating agent include dinitrophenyl-lysine (DNP-Lys) and the like.
  • Each reagent in the test kit of the present invention may be contained in a separate container, or may be contained in the same container mixed or unmixed. In the latter case, the test kit of the present invention can also be referred to as a test reagent.
  • the substrate is contained, for example, in a container separate from the carrier and the detection reagent.
  • the cancer to be tested is not particularly limited, and for example, the description of the cancer marker and the test method of the present invention can be incorporated.
  • Breast cancer is preferable as the cancer to be tested.
  • the method for measuring a cancer marker of the present invention is a step of bringing a biological sample of a subject into contact with a cancer marker expression measuring reagent and measuring the expression level of the cancer marker in the biological sample.
  • the cancer marker comprises the cancer marker of the present invention.
  • the measuring method of the present invention is characterized by including a step of contacting a biological sample of a subject with a reagent for measuring the expression of a cancer marker and measuring the expression level of the cancer marker in the biological sample, and other steps. And the conditions are not particularly limited.
  • the measuring method of the present invention the description of the cancer marker, the test method, and the test kit of the present invention can be incorporated.
  • the screening method of the present invention is a screening method for a candidate substance for a cancer therapeutic drug, and includes a step of selecting an expression-suppressing substance that suppresses the expression of a cancer marker from a test substance as the candidate substance for treatment.
  • the cancer marker includes the cancer marker of the present invention.
  • the present invention is characterized in that the therapeutic drug candidate substance is selected based on the cancer marker of the present invention in the selection step, and other steps and conditions are not particularly limited.
  • the screening method of the present invention can be referred to the description of the cancer marker, the test method, the test kit, and the measurement method of the present invention.
  • the expression-suppressing substance examples include a substance that suppresses transcription of mRNA from the cancer marker gene, a substance that cleaves the transcribed mRNA, and a substance that suppresses translation of protein from mRNA.
  • Specific examples include RNA interfering agents such as siRNA, antisense, and ribozymes.
  • test substance is not particularly limited, and is, for example, at least one selected from the group consisting of low molecular weight compounds, peptides, proteins and nucleic acids.
  • the method for screening the expression-suppressing substance of the present invention includes, for example, a step (expression step) in which the test substance is allowed to coexist in the expression system of the cancer marker of the present invention to express the cancer marker of the present invention, and the expression thereof.
  • the expression to be detected may be, for example, expression of the cancer marker protein of the present invention or transcription of mRNA of the cancer marker gene of the present invention.
  • the method for detecting the expression of the protein and the expression of mRNA is not particularly limited, and the above description can be incorporated.
  • the cancer marker consists of a group consisting of anti-HIRI P3 antibody, anti-FNDC11 antibody, anti-SLC1A3 antibody, anti-TMEM33 antibody, anti-ABCF1 antibody, anti-CFDP1 antibody, anti-POLR3GL antibody, anti-CADM1 antibody, anti-RNF128 antibody, and anti-ATP6V1B1 antibody.
  • the screening method of the present invention is, for example, a step of administering the test substance to a living body (administration step) and a step of expressing the cancer marker in the living body (expression).
  • Step) the step of obtaining a biological sample from the living body after the administration, the step of measuring the expression of the cancer marker in the biological sample, and the expression level of the cancer marker in the biological sample are the same as the test substance. It includes a step of selecting the test substance, which is lower than the biological sample derived from the control not administered, as the therapeutic candidate substance.
  • the administration conditions of the test substance to be administered to the living body in the administration step can be appropriately set according to the type of the test substance. Examples of the living body include humans and non-human animals other than humans, and examples of the non-human animals include mammals such as mice, rats, dogs, monkeys, rabbits, sheep and horses.
  • the expression of the cancer marker can be carried out, for example, by immunizing the living body with a protein corresponding to the cancer marker.
  • examples of the biological sample include the blood sample.
  • the cancer marker is a protein or gene of at least one cancer marker selected from the group consisting of HIRIP3, FNDC11, SLC1A3, TMEM33, ABCF1, CFDP1, POLR3GL, CADM1, RNF128, and ATP6V1B1, the present invention.
  • the screening method includes, for example, a step of coexisting the test substance in the expression system of the cancer marker to express the cancer marker, a step of detecting the expression of the cancer marker in the expression system, and the cancer marker.
  • the expression level of the test substance is lower than that of the control expression system in which the test substance does not coexist, and the step of selecting the test substance as the therapeutic candidate substance is included.
  • Example 1 The antibody titer of the antibody of the present invention (autoantibody against the cancer marker of the present invention) was measured in the sera of breast cancer patients and healthy subjects.
  • HIRIP3, FNDC11, SLC1A3, TMEM33, ABCF1, CFDP1, POLR3GL, CADM1, RNF128, and ATP6V1B1 were synthesized using a wheat cell-free protein synthesis system.
  • the wheat cell-free protein synthesis was carried out according to the method described in Reference 1 below.
  • a sequence encoding a His tag and a bls tag was added to the amino terminus in advance to the DNA template of each self-antigen protein.
  • TP53 which is a breast cancer marker
  • Reference 1 Takai, K et.al. ,. “Practical cell-free protein synthesis system using purified wheat embryos.” Nat Protoc. 2010, volume 5, pages 227-238
  • Reference 2 Sawasaki, Tet.al. “Arabidopsis HY5 protein functions as a DNA-binding tag for purification and functional immobilization of proteins on agarose / DNA microplate.”, FEBS Letters, 2008, volume 582, pages 221-228
  • a diluent 100 mmol / L Tris-HCl, pH8.0, 0.01% Tween20, 1 mg
  • a diluent 100 mmol / L Tris-HCl, pH8.0, 0.01% Tween20, 1 mg
  • FIG. 1 is a graph showing the antibody titer of each antigen, (A) is an overall view of the graph, and (B) is an enlarged view of the vertical axis of the corresponding graph of (A).
  • the vertical axis shows the signal intensity (antibody titer) of AlphaScreen
  • the left side shows the results of serum samples of healthy subjects
  • the right side shows the results of serum samples of breast cancer patients.
  • breast cancer patients have significant signal intensities of autoantibodies to serum HIRIP3, FNDC11, SLC1A3, TMEM33, ABCF1, CFDP1, POLR3GL, CADM1, RNF128, and ATP6V1B1 as compared to healthy subjects. It was expensive.
  • the signal intensity of autoantibodies against HIRIP3, FNDC11, SLC1A3, and TMEM33 is particularly high, and the antibody titer signal ratio of breast cancer patients / healthy subjects is higher than that of autoantibodies against TP53, which is a breast cancer marker, and p53 as a breast cancer marker. It was found that it can be used favorably in comparison with. From these facts, it was found that the cancer marker of the present invention serves as a marker for breast cancer.
  • Example 2 Changes in the antibody titer of the antibody of the present invention (autoantibody against the cancer marker of the present invention) depending on the stage of breast cancer were confirmed.
  • the stages of breast cancer patients with respect to the four cancer markers (anti-HIRI P3 antibody, anti-FNDC11 antibody, anti-SLC1A3 antibody, and anti-TMEM33 antibody) and comparative example (anti-TP53 antibody) having high antibody titer signal ratios in Example 1
  • stage classification of breast cancer is shown in Table 1 and FIG. 2 below.
  • FIG. 2 is a graph showing the antibody titer against each antigen at each stage.
  • the upper part shows the entire graph
  • the lower part is an enlarged view of the vertical axis of the upper graph.
  • the vertical axis shows the signal intensity (antibody titer) of AlphaScreen
  • the horizontal axis shows the control group, stage 0, stage I, stage II, and stage III serum samples from the left.
  • autoantibodies to HIRIP3, FNDC11, SLC1A3, and TMEM33 showed high signaling in any stage of breast cancer.
  • the antibody titer in stage 0 breast cancer was higher than that of autoantibodies against TP53.
  • the cancer marker of the present invention can be used as an early diagnostic marker for breast cancer. As described above, stage 0 breast cancer is difficult to detect early because no lumps or abnormal shadows are observed in diagnostic imaging. However, according to the cancer marker of the present invention, for example, early diagnosis of breast cancer Is possible.
  • Example 3 The relationship between the subtype of breast cancer and the antibody titer of the antibody of the present invention (autoantibody against the cancer marker of the present invention) was confirmed.
  • Luminal A 4131
  • Triple negative 58
  • FIG. 3 shows the antibody titer against each antigen in each breast cancer subtype.
  • the upper part shows the entire graph
  • the lower part is an enlarged view of the vertical axis of the upper graph.
  • the vertical axis shows the signal intensity (antibody titer) of AlphaScreen
  • the horizontal axis shows the control group, Luminal A (A), Luminal B (B), Her2 (H), and Her2 (H) from the left.
  • a serum sample of Triple negative (T) is shown.
  • FIG. 3 it was confirmed that autoantibodies against HIRIP3, FNDC11, SLC1A3, and TMEM33 showed high signals and were expressed in all subtypes of breast cancer.
  • the antibody titer signal ratio of breast cancer patients / healthy subjects was higher than that of autoantibodies against TP53, which is a breast cancer marker, and it can be preferably used. From these facts, it was found that the cancer marker of the present invention can be used regardless of the subtype of breast cancer.
  • Example 4 Tissue immunostaining confirmed that the cancer marker of the present invention, HIRIP3, was expressed in breast cancer tissue.
  • test samples were prepared from breast cancer tissue embedded in formalin-fixed paraffin for 40 patients stored at the Department of Pathology, Kanagawa Cancer Center, and deparaffinized and rehydrated to prepare test samples. .. Then, the test sample was treated with a high-pressure steam sterilizer for 15 minutes in a state of being immersed in a citric acid buffer (pH 6) to activate the antigenicity. After the activation, it is washed with phosphate buffer (PBS) and then immersed in 3% hydrogen peroxide solution for 5 minutes to inactivate endogenous peroxidase and with phosphate buffered saline (PBS). It was washed.
  • PBS phosphate buffer
  • PBS phosphate buffer
  • test sample was reacted with a 1700-fold diluted anti-rabbit HIRIP3 polyclonal antibody (Sigma-Aldrich, HPA063205) for 1 hour at room temperature, and washed with the PBS.
  • test sample was reacted with the HRP-labeled secondary antibody "Histfine Simple Stain MAX-PO (MULTI)" (Nichirei Bioscience, 724152) for 30 minutes at room temperature.
  • MULTI Simple Stain MAX-PO
  • test sample was washed with the PBS and colored with the "DAB Substrate Kit” (Nichirei Bioscience, 725191). Then, the test sample was washed with running water and nuclear-stained with hematoxylin.
  • test sample was washed with running water, dehydrated and cleared with 99.5% ethanol and 100% xylene. Then, the test sample was sealed with marinol, and the expression region of HIRIP3 stained brown by DAB was observed using an optical microscope (BX53, manufactured by Olympus Corporation).
  • FIG. 4 is a tissue staining diagram showing the expression of HIRIP3 in breast cancer tissue, (A) shows the central part of the cancer (Tumor Center Area), and (B) shows the infiltration tip of the cancer (Tumor Invasion Front). ) Is shown. Further, in FIG. 4B, the region surrounded by the line indicated by the arrow is the region where the cancer cells are present.
  • the upper diagram is a stained diagram of the HE-stained tissue, and the lower diagram is a DAB-stained stained diagram.
  • HIRIP3 was localized in the nucleus of breast cancer tissue. Further, as shown in the lower figure of FIG. 4 (B), it was found that the expression level of HIRIP3 was lower in the normal tissue than in the breast cancer tissue.
  • Tissue immunostaining confirmed that the cancer marker of the present invention was expressed in various cancer tissues.
  • Example 4 Same as Example 4 except that the tissue array of formalin-fixed paraffin-embedded tissue owned by the Kanagawa Cancer Center was used and the test samples were breast cancer (metastasis or primary lesion), lung cancer, and ovarian cancer. Then, immunostaining was performed. Then, in each test sample, the number of samples was counted as immunostaining positive (IHC +) when the area of the staining site was 5% or more and immunostaining negative (IHC-) when the area of the staining site was less than 5%. , The ratio of IHC + to the number of samples was calculated.
  • IHC + immunostaining positive
  • IHC- immunostaining negative
  • FIG. 5 is a graph showing the ratio of IHC + for each type of cancer in each test sample.
  • HIRIP3 was confirmed to be expressed in 66% in breast cancer (metastasis), 41% in breast cancer (primary lesion), 20% in lung cancer, and 23% in ovarian cancer. From these facts, it was found that HIRIP3 can be used as a cancer marker for breast cancer, lung cancer, and ovarian cancer.
  • the proportion of IHC + is particularly high in the metastatic lesions of breast cancer, it was found that it can be suitably used as a cancer marker for metastatic lesions of breast cancer.
  • Tissue immunostaining confirmed that the cancer marker of the present invention, SLC1A3, was expressed in breast cancer tissue.
  • the test sample was breast cancer tissue and normal mammary gland
  • the antibody reacting with the test sample was an anti-rabbit SLC1A3 polyclonal antibody (abcam, ab41751)
  • the antibody dilution ratio was set to 50 times in the same manner as in Example 4.
  • the expression region of SLC1A3 was observed using an optical microscope.
  • FIG. 6 is a tissue staining diagram showing the expression of SLC1A3 in normal mammary gland and breast cancer tissue, and from the left, HE staining diagram of breast cancer tissue, DAB staining diagram of breast cancer tissue, and DAB staining diagram of normal mammary gland. Further, in FIG. 6, the region surrounded by the line indicated by the arrow is the region where SLC1A3 is expressed. The upper and lower figures of FIG. 6 are similar except that different samples are used. As shown in FIG. 6, SLC1A3 was found to be more expressed in breast cancer tissues than in normal mammary glands.
  • Example 7 The antibody titer of the antibody of the present invention (autoantibody against the cancer marker of the present invention) was measured in the sera of breast cancer patients and healthy subjects.
  • the antibody titer of the antibody of the present invention (autoantibody against the marker of the present invention) was measured in the serum of the patient. In addition, when the distribution of antibody titers was confirmed, they were not normally distributed. Therefore, considering the ages of breast cancer patients and healthy subjects, the average value corrected for the effect of this was calculated, and the average value was calculated by analysis of covariance (ANCOVA). Was compared. In each of the following examples, the same statistical processing is performed. The result is shown in FIG.
  • FIG. 7 is a graph showing the antibody titer of each antigen.
  • the vertical axis shows the signal intensity (antibody titer) of AlphaScreen
  • the left side shows the results of serum samples of healthy subjects (control group)
  • the right side shows the results of serum samples of breast cancer patients (patient group).
  • breast cancer patients have significantly higher signal intensities of autoantibodies to FNDC11, SLC1A3, HIRIP3, and TMEM33 in serum than healthy subjects (p ⁇ 0.0001), and are suitable as breast cancer markers. It turns out that it can be used. From these facts, it was found that the cancer marker of the present invention serves as a marker for breast cancer.
  • Example 8 Changes in the antibody titer of the antibody of the present invention (autoantibody against the cancer marker of the present invention) depending on the stage of breast cancer were confirmed.
  • the change in the antibody titer of the cancer marker of the present invention was confirmed depending on the stage of breast cancer in the same manner as in Example 2 except that the sample used in Example 7 was used.
  • FIG. 8 is a graph showing the antibody titer against each antigen at each stage.
  • the vertical axis shows the signal intensity (antibody titer) of AlphaScreen
  • the horizontal axis shows the control group, stage 0, stage I, stage II, and stage III serum samples from the left.
  • autoantibodies to FNDC11, SLC1A3, HIRIP3, and TMEM33 showed high signaling in any stage of breast cancer. From these facts, it was found that the cancer marker of the present invention can be used as an early diagnostic marker for breast cancer. As described above, stage 0 breast cancer is difficult to detect early because no lumps or abnormal shadows are observed in diagnostic imaging. However, according to the cancer marker of the present invention, for example, early diagnosis of breast cancer Is possible.
  • Example 9 The relationship between the subtype of breast cancer and the antibody titer of the antibody of the present invention (autoantibody against the cancer marker of the present invention) was confirmed.
  • Example 7 The relationship between the breast cancer subtype and the antibody titer of the cancer marker of the present invention was confirmed in the same manner as in Example 3 except that the sample used in Example 7 was used.
  • FIG. 9 shows the antibody titer against each antigen in each breast cancer subtype.
  • the vertical axis shows the signal intensity (antibody titer) of AlphaScreen
  • the horizontal axis shows the serum samples of the control group, Her2, Luminal A, Luminal B, and Triple negative from the left.
  • autoantibodies to FNDC11, SLC1A3, HIRIP3, and TMEM33 showed high signals and were expressed in all subtypes of breast cancer. From these facts, it was found that the cancer marker of the present invention can be used regardless of the subtype of breast cancer.
  • the antibody titer against the self-antigen protein in each subtype is diagnosed for each subtype by performing ROC analysis and calculating the sensitivity, specificity, and area under the ROC curve (AUC: area under the curve). I evaluated the ability. The results are shown in Tables 3 to 6 below.
  • autoantibodies against FNDC11, SLC1A3, HIRIP3, and TMEM33 can all detect each subtype of breast cancer with high sensitivity.
  • the autoantibody against FNDC11 has an AUC of 0.877 to 0.897 in each subtype
  • the autoantibody against TMEM33 has an AUC of 0.861 to 0.882 in each subtype. It was found that it has extremely high diagnostic ability for breast cancer.
  • Example 10 The relationship of the present invention (autoantibody against the cancer marker of the present invention) was confirmed between the initial breast cancer and the recurrent breast cancer.
  • the cancer marker of the present invention can be used as a diagnostic marker for both initial breast cancer and recurrent breast cancer.
  • Many of the existing breast cancer markers are not suitable for detecting the first breast cancer, and it is known that TP53, which is an existing breast cancer marker capable of detecting the first breast cancer, detects cancers other than breast cancer. There is. Therefore, according to the cancer marker of the present invention, for example, early diagnosis of initial breast cancer becomes possible.
  • Appendix Some or all of the above embodiments and examples may be described as, but not limited to, the following appendices.
  • (Appendix 1) Anti-HIRIP3 antibody, HIRIP3, anti-FNDC11 antibody, FNDC11, anti-SLC1A3 antibody, SLC1A3, anti-TMEM33 antibody, TMEM33, anti-ABCF1 antibody, ABCF1, anti-CFDP1 antibody, CFDP1, anti-POLR3GL antibody, POLR3GL, anti-CADM1 antibody, CAL M1
  • a cancer marker comprising at least one selected from the group consisting of antibody, RNF128, anti-ATP6V1B1 antibody, and ATP6V1B1.
  • Appendix 2 Anti-human-derived HIRIP3 antibody, anti-human-derived FNDC11 antibody, anti-human-derived SLC1A3 antibody, anti-human-derived TMEM33 antibody, anti-human-derived ABCF1 antibody, anti-human-derived CFDP1 antibody, anti-human-derived POLR3GL antibody, anti-human-derived CADM1 antibody, anti-human
  • the cancer marker according to Appendix 1 or 2 which comprises at least one antibody selected from the group consisting of anti-human-derived HIRIP3 antibody, anti-human-derived FNDC11 antibody, anti-human-derived SLC1A3 antibody, and anti-human-derived TMEM33 antibody.
  • the cancer is selected from the group consisting of breast cancer, ovarian cancer, pancreatic cancer, liver cancer, bile duct cancer, colon cancer, colon cancer, rectal cancer, stomach cancer, oral cancer, and lung cancer.
  • the cancer marker according to any one of Appendix 1 to 3 which is at least one cancer.
  • Appendix 5 The cancer marker according to any one of Appendix 1 to 4, wherein the cancer is breast cancer.
  • the cancer markers include anti-HIRIP3 antibody, HIRIP3, anti-FNDC11 antibody, FNDC11, anti-SLC1A3 antibody, SLC1A3, anti-TMEM33 antibody, TMEM33, anti-ABCF1 antibody, ABCF1, anti-CFDP1 antibody, CFDP1, anti-POLR3GL antibody, POLR3GL, anti-CAMM1
  • a method for testing the risk of developing cancer comprising at least one selected from the group consisting of antibody, CADM1, anti-RNF128 antibody, RNF128, anti-ATP6V1B1 antibody, and ATP6V1B1.
  • the cancer markers include anti-human-derived HIRIP3 antibody, anti-human-derived FNDC11 antibody, anti-human-derived SLC1A3 antibody, anti-human-derived TMEM33 antibody, anti-human-derived ABCF1 antibody, anti-human-derived CFDP1 antibody, anti-human-derived POLR3GL antibody, and anti-human.
  • Test method. The cancer is selected from the group consisting of breast cancer, ovarian cancer, pancreatic cancer, liver cancer, bile duct cancer, colon cancer, colon cancer, rectal cancer, stomach cancer, oral cancer, and lung cancer.
  • Appendix 10 The test method according to any one of Appendix 6 to 9, wherein the cancer is breast cancer.
  • (Appendix 11) The test method according to any one of Appendix 6 to 10, wherein the biological sample is a blood sample.
  • (Appendix 12) Contains reagents for measuring the expression of cancer markers
  • the cancer markers include anti-HIRIP3 antibody, HIRIP3, anti-FNDC11 antibody, FNDC11, anti-SLC1A3 antibody, SLC1A3, anti-TMEM33 antibody, TMEM33, anti-ABCF1 antibody, ABCF1, anti-CFDP1 antibody, CFDP1, anti-POLR3GL antibody, POLR3GL, anti-CAMM1
  • a cancer test kit comprising at least one selected from the group consisting of antibody, CADM1, anti-RNF128 antibody, RNF128, anti-ATP6V1B1 antibody, and ATP6V1B1.
  • the cancer marker consists of a group consisting of anti-HIRI P3 antibody, anti-FNDC11 antibody, anti-SLC1A3 antibody, anti-TMEM33 antibody, anti-ABCF1 antibody, anti-CFDP1 antibody, anti-POLR3GL antibody, anti-CADM1 antibody, anti-RNF128 antibody, and anti-ATP6V1B1 antibody. At least one antibody of choice,
  • the cancer marker is a protein of at least one cancer marker selected from the group consisting of HIRIP3, FNDC11, SLC1A3, TMEM33, ABCF1, CFDP1, POLR3GL, CADM1, RNF128, and ATP6V1B1.
  • the cancer marker is a gene for at least one cancer marker selected from the group consisting of HIRIP3, FNDC11, SLC1A3, TMEM33, ABCF1, CFDP1, POLR3GL, CADM1, RNF128, and ATP6V1B1.
  • the test kit according to Appendix 12, wherein the expression measurement reagent is a reagent that amplifies the mRNA of a cancer marker gene by reverse transcription.
  • the cancer is selected from the group consisting of breast cancer, ovarian cancer, pancreatic cancer, liver cancer, bile duct cancer, colon cancer, colon cancer, rectal cancer, stomach cancer, oral cancer, and lung cancer.
  • the cancer markers include anti-HIRIP3 antibody, HIRIP3, anti-FNDC11 antibody, FNDC11, anti-SLC1A3 antibody, SLC1A3, anti-TMEM33 antibody, TMEM33, anti-ABCF1 antibody, ABCF1, anti-CFDP1 antibody, CFDP1, anti-POLR3GL antibody, POLR3GL, anti-CAMM1
  • a method for measuring a cancer marker comprising at least one selected from the group consisting of antibody, CADM1, anti-RNF128 antibody, RNF128, anti-ATP6V1B1 antibody, and ATP6V1B1.
  • the cancer marker consists of a group consisting of anti-HIRI P3 antibody, anti-FNDC11 antibody, anti-SLC1A3 antibody, anti-TMEM33 antibody, anti-ABCF1 antibody, anti-CFDP1 antibody, anti-POLR3GL antibody, anti-CADM1 antibody, anti-RNF128 antibody, and anti-ATP6V1B1 antibody.
  • the expression measuring reagent includes an antigen corresponding to the cancer marker and a detection reagent for detecting the cancer marker.
  • the measuring method according to Appendix 22 which includes a step of measuring the complex.
  • Appendix 24 The measuring method according to Appendix 23, wherein the detection reagent is labeled.
  • Appendix 25 The measuring method according to Appendix 23 or 24, wherein the detection reagent is an antibody that recognizes an antibody that is a cancer marker.
  • Appendix 26 The measuring method according to any one of Appendix 23 to 25, wherein the antigen corresponding to the cancer marker is immobilized on a carrier.
  • the cancer marker is a protein of at least one cancer marker selected from the group consisting of HIRIP3, FNDC11, SLC1A3, TMEM33, ABCF1, CFDP1, POLR3GL, CADM1, RNF128, and ATP6V1B1.
  • the expression measuring reagent includes a substance that binds to the protein of the cancer marker and a binding detection reagent that detects the binding between the protein of the cancer marker and the binding substance.
  • the cancer marker is a gene for at least one cancer marker selected from the group consisting of HIRIP3, FNDC11, SLC1A3, TMEM33, ABCF1, CFDP1, POLR3GL, CADM1, RNF128, and ATP6V1B1.
  • the expression measurement reagent is a reagent that amplifies the mRNA of a cancer marker gene by reverse transcription. A step of amplifying the gene of the cancer marker after contacting the biological sample of the subject with the expression measurement reagent, and 22.
  • the measuring method according to Appendix 22 which includes a step of measuring the obtained amplified product.
  • the cancer is selected from the group consisting of breast cancer, ovarian cancer, pancreatic cancer, liver cancer, bile duct cancer, colon cancer, colon cancer, rectal cancer, stomach cancer, oral cancer, and lung cancer.
  • a step of selecting an expression-suppressing substance that suppresses the expression of a cancer marker from a test substance as a therapeutic candidate substance is included.
  • the cancer markers include anti-HIRIP3 antibody, HIRIP3, anti-FNDC11 antibody, FNDC11, anti-SLC1A3 antibody, SLC1A3, anti-TMEM33 antibody, TMEM33, anti-ABCF1 antibody, ABCF1, anti-CFDP1 antibody, CFDP1, anti-POLR3GL antibody, POLR3GL, anti-CAMM1
  • a method for screening a candidate substance for a cancer therapeutic agent which comprises at least one selected from the group consisting of antibody, CADM1, anti-RNF128 antibody, RNF128, anti-ATP6V1B1 antibody, and ATP6V1B1.
  • the cancer marker consists of a group consisting of anti-HIRI P3 antibody, anti-FNDC11 antibody, anti-SLC1A3 antibody, anti-TMEM33 antibody, anti-ABCF1 antibody, anti-CFDP1 antibody, anti-POLR3GL antibody, anti-CADM1 antibody, anti-RNF128 antibody, and anti-ATP6V1B1 antibody.
  • At least one antibody of choice The step of administering the test substance to a living body and The step of expressing the cancer marker in the living body and The step of obtaining a biological sample from the living body after the administration and The step of measuring the expression of a cancer marker in the biological sample and Addendum 31 including a step of selecting the test substance whose expression level of the cancer marker in the biological sample is lower than that of the control-derived biological sample to which the test substance is not administered as the therapeutic candidate substance.
  • the cancer marker is a protein or gene of at least one cancer marker selected from the group consisting of HIRIP3, FNDC11, SLC1A3, TMEM33, ABCF1, CFDP1, POLR3GL, CADM1, RNF128, and ATP6V1B1.
  • a step of coexisting the test substance in the expression system of the cancer marker to express the cancer marker a step of detecting the expression of the cancer marker in the expression system, and a step of detecting the expression of the cancer marker in the expression system.
  • the screening method according to Appendix 31 which comprises a step of selecting the test substance whose expression level of the cancer marker is lower than that of the control expression system in which the test substance does not coexist as the therapeutic candidate substance. ..
  • (Appendix 34) The screening method according to any one of Appendix 31 to 33, wherein the test substance is at least one selected from the group consisting of low molecular weight compounds, peptides, proteins and nucleic acids.
  • the risk of developing cancer in a subject can be tested by measuring the expression level of the marker of the present invention.
  • a candidate substance for the treatment of cancer can be obtained by screening using the marker of the present invention. Therefore, the present invention is extremely useful in the clinical and biochemical fields.

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Abstract

Provided is a novel cancer marker for testing the risk of developing a cancer.　This cancer marker includes at least one substance selected from the group consisting of anti-HIRIP3 antibodies, HIRIP3, anti-FNDC11 antibodies, FNDC11, anti-SLC1A3 antibodies, SLC1A3, anti-TMEM33 antibodies, TMEM33, anti-ABCF1 antibodies, ABCF1, anti-CFDP1 antibodies, CFDP1, anti-POLR3GL antibodies, POLR3GL, anti-CADM1 antibodies, CADM1, anti-RNF128 antibodies, RNF128, anti-ATP6V1B1 antibodies, and ATP6V1B1.

Description

がんマーカーおよびその用途Cancer markers and their uses
　本発明は、がんマーカー、それを用いたがんの罹患危険度の試験方法、がんの試験キット、およびがんマーカーの測定方法に関し、さらに、がん治療薬のスクリーニング方法に関する。 The present invention relates to a cancer marker, a method for testing the risk of developing cancer using the marker, a test kit for cancer, a method for measuring the cancer marker, and a method for screening a cancer therapeutic agent.
　近年、がんは、日本人の死因のトップであり、他の国においても、死因の上位を占めるに致っている。がんの発生および進展には、遺伝的要因、環境的要因等の様々な因子が関連しているが、決定的な診断方法および治療法は、未だ確立されていない。 In recent years, cancer has become the leading cause of death in Japan, and has become the leading cause of death in other countries as well. Although various factors such as genetic factors and environmental factors are associated with the development and progression of cancer, definitive diagnostic and therapeutic methods have not yet been established.
　がんの中でも、例えば、乳がんは、日本人女性の罹患率が最も高いがんであり、その罹患率は年々増加傾向にある。乳がんの検診は、触診やマンモグラフィーが主流であり、診察で判明したときには腫瘍が大きくなり、他の組織に転移している可能性が高い。また、２０～３０歳代女性の乳腺が発達している乳房においては、発見が困難である。このため、乳がんをはじめとする各種がんについて、早期発見を可能とするためのがんマーカーの開発が望まれている（非特許文献１～６）。 Among cancers, for example, breast cancer has the highest prevalence among Japanese women, and the prevalence is increasing year by year. Palpation and mammography are the mainstream of breast cancer screening, and when the examination reveals that the tumor has grown, it is likely that it has spread to other tissues. In addition, it is difficult to detect in the breast where the mammary gland of women in their 20s and 30s is developed. For this reason, it is desired to develop a cancer marker that enables early detection of various cancers including breast cancer (Non-Patent Documents 1 to 6).
　そこで、本発明は、がんの罹患危険度を試験するための新たながんマーカーの提供を目的とする。 Therefore, an object of the present invention is to provide a new cancer marker for testing the risk of developing cancer.
　本発明のがんマーカーは、抗ＨＩＲＩＰ３抗体、ＨＩＲＩＰ３、抗ＦＮＤＣ１１抗体、ＦＮＤＣ１１、抗ＳＬＣ１Ａ３抗体、ＳＬＣ１Ａ３、抗ＴＭＥＭ３３抗体、ＴＭＥＭ３３、抗ＡＢＣＦ１抗体、ＡＢＣＦ１、抗ＣＦＤＰ１抗体、ＣＦＤＰ１、抗ＰＯＬＲ３ＧＬ抗体、ＰＯＬＲ３ＧＬ、抗ＣＡＤＭ１抗体、ＣＡＤＭ１、抗ＲＮＦ１２８抗体、ＲＮＦ１２８、抗ＡＴＰ６Ｖ１Ｂ１抗体、およびＡＴＰ６Ｖ１Ｂ１からなる群から選択される少なくとも１つを含む。 The cancer markers of the present invention include anti-HIRIP3 antibody, HIRIP3, anti-FNDC11 antibody, FNDC11, anti-SLC1A3 antibody, SLC1A3, anti-TMEM33 antibody, TMEM33, anti-ABCF1 antibody, ABCF1, anti-CFDP1 antibody, CFDP1, anti-POLR3GL antibody, POLR3GL It comprises at least one selected from the group consisting of anti-CADM1 antibody, CADM1, anti-RNF128 antibody, RNF128, anti-ATP6V1B1 antibody, and ATP6V1B1.
　本発明のがんの罹患危険度の試験方法は、被検者の生体試料におけるがんマーカーの発現量を測定する工程を含み、
前記がんマーカーは、抗ＨＩＲＩＰ３抗体、ＨＩＲＩＰ３、抗ＦＮＤＣ１１抗体、ＦＮＤＣ１１、抗ＳＬＣ１Ａ３抗体、ＳＬＣ１Ａ３、抗ＴＭＥＭ３３抗体、ＴＭＥＭ３３、抗ＡＢＣＦ１抗体、ＡＢＣＦ１、抗ＣＦＤＰ１抗体、ＣＦＤＰ１、抗ＰＯＬＲ３ＧＬ抗体、ＰＯＬＲ３ＧＬ、抗ＣＡＤＭ１抗体、ＣＡＤＭ１、抗ＲＮＦ１２８抗体、ＲＮＦ１２８、抗ＡＴＰ６Ｖ１Ｂ１抗体、およびＡＴＰ６Ｖ１Ｂ１からなる群から選択される少なくとも１つをを含む。 The method for testing the risk of developing cancer of the present invention includes a step of measuring the expression level of a cancer marker in a biological sample of a subject.
The cancer markers include anti-HIRIP3 antibody, HIRIP3, anti-FNDC11 antibody, FNDC11, anti-SLC1A3 antibody, SLC1A3, anti-TMEM33 antibody, TMEM33, anti-ABCF1 antibody, ABCF1, anti-CFDP1 antibody, CFDP1, anti-POLR3GL antibody, POLR3GL, anti-CAMM1 Includes at least one selected from the group consisting of antibody, CADM1, anti-RNF128 antibody, RNF128, anti-ATP6V1B1 antibody, and ATP6V1B1.
　本発明のがんの試験キットは、がんマーカーの発現測定試薬を含み、
前記がんマーカーは、抗ＨＩＲＩＰ３抗体、ＨＩＲＩＰ３、抗ＦＮＤＣ１１抗体、ＦＮＤＣ１１、抗ＳＬＣ１Ａ３抗体、ＳＬＣ１Ａ３、抗ＴＭＥＭ３３抗体、ＴＭＥＭ３３、抗ＡＢＣＦ１抗体、ＡＢＣＦ１、抗ＣＦＤＰ１抗体、ＣＦＤＰ１、抗ＰＯＬＲ３ＧＬ抗体、ＰＯＬＲ３ＧＬ、抗ＣＡＤＭ１抗体、ＣＡＤＭ１、抗ＲＮＦ１２８抗体、ＲＮＦ１２８、抗ＡＴＰ６Ｖ１Ｂ１抗体、およびＡＴＰ６Ｖ１Ｂ１からなる群から選択される少なくとも１つを含む。 The cancer test kit of the present invention contains a reagent for measuring the expression of a cancer marker.
The cancer markers include anti-HIRIP3 antibody, HIRIP3, anti-FNDC11 antibody, FNDC11, anti-SLC1A3 antibody, SLC1A3, anti-TMEM33 antibody, TMEM33, anti-ABCF1 antibody, ABCF1, anti-CFDP1 antibody, CFDP1, anti-POLR3GL antibody, POLR3GL, anti-CAMM1 Includes at least one selected from the group consisting of antibody, CADM1, anti-RNF128 antibody, RNF128, anti-ATP6V1B1 antibody, and ATP6V1B1.
　本発明のがんマーカーの測定方法は、被検者の生体試料と、がんマーカーの発現測定試薬とを接触させ、前記生体試料におけるがんマーカーの発現量を測定する工程を含み、
前記がんマーカーは、抗ＨＩＲＩＰ３抗体、ＨＩＲＩＰ３、抗ＦＮＤＣ１１抗体、ＦＮＤＣ１１、抗ＳＬＣ１Ａ３抗体、ＳＬＣ１Ａ３、抗ＴＭＥＭ３３抗体、ＴＭＥＭ３３、抗ＡＢＣＦ１抗体、ＡＢＣＦ１、抗ＣＦＤＰ１抗体、ＣＦＤＰ１、抗ＰＯＬＲ３ＧＬ抗体、ＰＯＬＲ３ＧＬ、抗ＣＡＤＭ１抗体、ＣＡＤＭ１、抗ＲＮＦ１２８抗体、ＲＮＦ１２８、抗ＡＴＰ６Ｖ１Ｂ１抗体、およびＡＴＰ６Ｖ１Ｂ１からなる群から選択される少なくとも１つを含む。 The method for measuring a cancer marker of the present invention includes a step of contacting a biological sample of a subject with a reagent for measuring the expression of a cancer marker and measuring the expression level of the cancer marker in the biological sample.
The cancer markers include anti-HIRIP3 antibody, HIRIP3, anti-FNDC11 antibody, FNDC11, anti-SLC1A3 antibody, SLC1A3, anti-TMEM33 antibody, TMEM33, anti-ABCF1 antibody, ABCF1, anti-CFDP1 antibody, CFDP1, anti-POLR3GL antibody, POLR3GL, anti-CAMM1 Includes at least one selected from the group consisting of antibody, CADM1, anti-RNF128 antibody, RNF128, anti-ATP6V1B1 antibody, and ATP6V1B1.
　本発明のがん治療薬の候補物質のスクリーニング方法は、被検物質から、がんマーカーの発現を抑制する発現抑制物質を、前記治療用候補物質として選択する工程を含み、
前記がんマーカーは、抗ＨＩＲＩＰ３抗体、ＨＩＲＩＰ３、抗ＦＮＤＣ１１抗体、ＦＮＤＣ１１、抗ＳＬＣ１Ａ３抗体、ＳＬＣ１Ａ３、抗ＴＭＥＭ３３抗体、ＴＭＥＭ３３、抗ＡＢＣＦ１抗体、ＡＢＣＦ１、抗ＣＦＤＰ１抗体、ＣＦＤＰ１、抗ＰＯＬＲ３ＧＬ抗体、ＰＯＬＲ３ＧＬ、抗ＣＡＤＭ１抗体、ＣＡＤＭ１、抗ＲＮＦ１２８抗体、ＲＮＦ１２８、抗ＡＴＰ６Ｖ１Ｂ１抗体、およびＡＴＰ６Ｖ１Ｂ１からなる群から選択される少なくとも１つを含む。 The method for screening a candidate substance for a cancer therapeutic agent of the present invention includes a step of selecting an expression-suppressing substance that suppresses the expression of a cancer marker from a test substance as the therapeutic candidate substance.
The cancer markers include anti-HIRIP3 antibody, HIRIP3, anti-FNDC11 antibody, FNDC11, anti-SLC1A3 antibody, SLC1A3, anti-TMEM33 antibody, TMEM33, anti-ABCF1 antibody, ABCF1, anti-CFDP1 antibody, CFDP1, anti-POLR3GL antibody, POLR3GL, anti-CAMM1 Includes at least one selected from the group consisting of antibody, CADM1, anti-RNF128 antibody, RNF128, anti-ATP6V1B1 antibody, and ATP6V1B1.
　本発明者は、鋭意研究の結果、生体におけるＨＩＲＩＰ３、ＦＮＤＣ１１、ＳＬＣ１Ａ３、ＴＭＥＭ３３、ＡＢＣＦ１、ＣＦＤＰ１、ＰＯＬＲ３ＧＬ、ＣＡＤＭ１、ＲＮＦ１２８、およびＡＴＰ６Ｖ１Ｂ１に対する自己抗体が、がんの発症と相関を示すことを見出し、本発明を確立するに至った。本発明のマーカーの発現量を測定することによって、被検者のがんの罹患危険度を試験できる。また、本発明のマーカーを用いたスクリーニングにより、がんの治療用候補物質を得ることもできる。このため、本発明は、臨床分野および生化学分野において極めて有用である。 As a result of diligent research, the present inventor has found that autoantibodies against HIRIP3, FNDC11, SLC1A3, TMEM33, ABCF1, CFDP1, POLR3GL, CADM1, RNF128, and ATP6V1B1 in vivo correlate with the onset of cancer. It came to establish the invention. By measuring the expression level of the marker of the present invention, the risk of developing cancer in a subject can be tested. In addition, a candidate substance for the treatment of cancer can be obtained by screening using the marker of the present invention. Therefore, the present invention is extremely useful in the clinical and biochemical fields.
図１は、実施例１のAlphaScreenの結果を示すグラフである。FIG. 1 is a graph showing the results of the Alpha Screen of Example 1. 図２は、実施例２のAlphaScreenの結果を示すグラフである。FIG. 2 is a graph showing the results of the Alpha Screen of Example 2. 図３は、実施例３のAlphaScreenの結果を示すグラフである。FIG. 3 is a graph showing the results of the Alpha Screen of Example 3. 図４は、実施例４の免疫染色の結果を示す写真である。FIG. 4 is a photograph showing the results of immunostaining of Example 4. 図５は、実施例５の免疫染色の結果を示すグラフである。FIG. 5 is a graph showing the results of immunostaining of Example 5. 図６は、実施例６の免疫染色の結果を示す写真である。FIG. 6 is a photograph showing the results of immunostaining of Example 6. 図７は、実施例７のAlphaScreenの結果を示すグラフである。FIG. 7 is a graph showing the results of the Alpha Screen of Example 7. 図８は、実施例８のAlphaScreenの結果を示すグラフである。FIG. 8 is a graph showing the results of the Alpha Screen of Example 8. 図９は、実施例９のAlphaScreenの結果を示すグラフである。FIG. 9 is a graph showing the results of the Alpha Screen of Example 9.
（がんマーカー）
　本発明のがんマーカーは、前述のように、抗ＨＩＲＩＰ３抗体、ＨＩＲＩＰ３、抗ＦＮＤＣ１１抗体、ＦＮＤＣ１１、抗ＳＬＣ１Ａ３抗体、ＳＬＣ１Ａ３、抗ＴＭＥＭ３３抗体、ＴＭＥＭ３３、抗ＡＢＣＦ１抗体、ＡＢＣＦ１、抗ＣＦＤＰ１抗体、ＣＦＤＰ１、抗ＰＯＬＲ３ＧＬ抗体、ＰＯＬＲ３ＧＬ、抗ＣＡＤＭ１抗体、ＣＡＤＭ１、抗ＲＮＦ１２８抗体、ＲＮＦ１２８、抗ＡＴＰ６Ｖ１Ｂ１抗体、およびＡＴＰ６Ｖ１Ｂ１からなる群から選択される少なくとも１つを含む。本発明のがんマーカーによれば、例えば、被検者の生体試料における前記がんマーカーの発現量を測定することで、前記被検者のがんの罹患危険度を試験できる。以下において、抗ＨＩＲＩＰ３抗体、抗ＦＮＤＣ１１抗体、抗ＳＬＣ１Ａ３抗体、抗ＴＭＥＭ３３抗体、抗ＡＢＣＦ１抗体、抗ＣＦＤＰ１抗体、抗ＰＯＬＲ３ＧＬ抗体、抗ＣＡＤＭ１抗体、抗ＲＮＦ１２８抗体、および、抗ＡＴＰ６Ｖ１Ｂ１抗体を、本発明の抗体ともいう。また、ＨＩＲＩＰ３、ＦＮＤＣ１１、ＳＬＣ１Ａ３、ＴＭＥＭ３３、ＡＢＣＦ１、ＣＦＤＰ１、ＰＯＬＲ３ＧＬ、ＣＡＤＭ１、ＲＮＦ１２８、および、ＡＴＰ６Ｖ１Ｂ１を、本発明の抗原タンパク質ともいう。 (Cancer marker)
As described above, the cancer markers of the present invention include anti-HIRI P3 antibody, HIRIP3, anti-FNDC11 antibody, FNDC11, anti-SLC1A3 antibody, SLC1A3, anti-TMEM33 antibody, TMEM33, anti-ABCF1 antibody, ABCF1, anti-CFDP1 antibody, CFDP1, anti. It comprises at least one selected from the group consisting of POLR3GL antibody, POLR3GL, anti-CADM1 antibody, CADM1, anti-RNF128 antibody, RNF128, anti-ATP6V1B1 antibody, and ATP6V1B1. According to the cancer marker of the present invention, for example, the risk of developing cancer in the subject can be tested by measuring the expression level of the cancer marker in the biological sample of the subject. In the following, anti-HIRIP3 antibody, anti-FNDC11 antibody, anti-SLC1A3 antibody, anti-TMEM33 antibody, anti-ABCF1 antibody, anti-CFDP1 antibody, anti-POLR3GL antibody, anti-CADM1 antibody, anti-RNF128 antibody, and anti-ATP6V1B1 antibody are used as antibodies of the present invention. Also called. Further, HIRIP3, FNDC11, SLC1A3, TMEM33, ABCF1, CFDP1, POLR3GL, CADM1, RNF128, and ATP6V1B1 are also referred to as antigen proteins of the present invention.
　本発明の抗体および抗原タンパク質の由来は、特に制限されず、例えば、被検者の種類によって適宜設定できる。前記由来は、例えば、ヒト、ヒトを除く非ヒト動物等があげられ、前記非ヒト動物は、例えば、マウス、ラット、イヌ、サル、ウサギ、ヒツジ、ウマ等の哺乳類があげられる。本発明の抗体および抗原タンパク質は、例えば、ヒト由来であることが好ましい。各種動物由来の前記抗体および抗原タンパク質は、例えば、既存のデータベースに登録されている情報を参照できる。 The origin of the antibody and antigen protein of the present invention is not particularly limited and can be appropriately set depending on the type of subject, for example. The origin includes, for example, humans, non-human animals other than humans, and examples of the non-human animals include mammals such as mice, rats, dogs, monkeys, rabbits, sheep, and horses. The antibody and antigen protein of the present invention are preferably derived from humans, for example. For the antibodies and antigen proteins derived from various animals, for example, information registered in an existing database can be referred to.
　本発明の抗体は、対応する抗原タンパク質に結合してもよいし、その部分配列からなるペプチド、すなわち、対応する抗原タンパク質のペプチド断片に結合してもよい。 The antibody of the present invention may bind to the corresponding antigen protein, or may bind to a peptide consisting of a partial sequence thereof, that is, a peptide fragment of the corresponding antigen protein.
　ヒト由来ＨＩＲＩＰ３は、ｃＤＮＡとして、例えば、ＮＣＢＩアクセッション番号NM_003609.4で登録されている下記の塩基配列（配列番号１）における下線部（492－2161番目）の領域（終始コドン含む）、タンパク質として、例えば、ＮＣＢＩアクセッション番号NP_003600.2で登録されている下記のアミノ酸配列（配列番号２）があげられる。配列番号１の塩基配列は、配列番号２のアミノ酸配列をコードする配列である。 Human-derived HIRIP3 can be used as a cDNA, for example, as a protein in the underlined region (492-2161) in the following nucleotide sequence (SEQ ID NO: 1) registered in NCBI Accession No. NM_003609.4. For example, the following amino acid sequence (SEQ ID NO: 2) registered under NCBI accession number NP_003600.2 can be mentioned. The base sequence of SEQ ID NO: 1 is a sequence encoding the amino acid sequence of SEQ ID NO: 2.
ヒト由来ＨＩＲＩＰ３　ｃＤＮＡ（配列番号１）
5'-GTAGCAGCGACGCGGTGACGCCACAAAAATGGCGGACGCTGGAAAGCGCCGTTCCTGACTCTAATGTACTTAGACACTTGAAGCCACAAAAGGATTTATCCCCGAGGTTCCTCATCTGCTCGCGAGGATGCCTTTTCTCTTCTGCCTTGCGAAATAACAGCAGCCTAGCTGTTGCCCGTGACCAGTGAGAAAGGCAGCGTCGCGGGCTGATTAGGTTTCACCCAAAGGGTGCCGGCGCCGAATTGGTTTCTAACGAGAACTTTTAAAATGATCCGTTCCAAAAAAGGGTAGGAGCCGCGAGACCCTCCAACTGCCCAGAGAAAACAAGTCTCGTCTGGCAAAGTTCTCGGCCCACGCGGTCCGCGGCCAAGGGCCAACGGTCCCTCGCCCCACGTTGCCGCAGCACTGCGCGTGCGCGAGCCGCTGTCAAACGCGCTGACGGAGGCCGAGAAGAAAAAAAGGCGGGAGCCGTCAATCCCGGGTTGAGCAAAATGGCGCGGGAGAAGGAGATGCAGGAGTTCACCCGTAGCTTCTTCCGAGGCCGCCCGGACCTCAGCACGCTTACGCATTCCATCGTGCGGCGGAGGTACTTAGCTCACTCGGGCCGCAGCCACCTGGAGCCCGAGGAGAAGCAGGCACTGAAGCGGCTGGTGGAGGAGGAGCTGCTGAAGATGCAGGTGGATGAAGCCGCTTCCAGGGAAGACAAACTGGACCTTACCAAGAAGGGCAAGAGGCCTCCCACCCCTTGTAGCGACCCGGAGAGAAAAAGGTTCCGCTTCAATTCAGAGTCGGAGTCCGGCTCTGAAGCCTCCAGCCCAGACTACTTTGGACCCCCAGCAAAGAATGGGGTGGCAGCAGAAGTCAGCCCAGCCAAAGAGGAGAATCCAAGGCGAGCCTCAAAGGCAGTTGAGGAGAGCAGTGATGAGGAACGGCAGAGGGACCTGCCCGCACAGAGGGGAGAGGAGAGCAGTGAGGAGGAGGAAAAGGGGTACAAGGGGAAGACTAGGAAGAAACCTGTGGTAAAGAAGCAGGCACCAGGCAAGGCCTCAGTCAGTAGGAAGCAGGCCAGGGAAGAAAGTGAGGAGAGCGAGGCAGAACCCGTTCAGAGGACAGCAAAGAAGGTGGAGGGAAATAAAGGAACTAAAAGCCTGAAGGAAAGTGAACAGGAGAGTGAAGAGGAGATCCTAGCCCAGAAGAAAGAGCAGAGAGAGGAGGAAGTGGAGGAGGAAGAGAAAGAAGAGGATGAGGAAAAGGGGGATTGGAAACCCAGAACCAGGAGCAATGGCCGGAGAAAGTCAGCTAGGGAGGAGAGGAGCTGTAAGCAGAAAAGCCAGGCAAAGAGGCTCTTGGGAGACTCAGACAGCGAGGAAGAGCAGAAAGAGGCAGCCAGCAGTGGGGATGACAGTGGGAGAGATAGAGAACCCCCAGTGCAGAGGAAGAGTGAGGACAGGACCCAGCTTAAGGGTGGGAAGAGGTTGAGTGGAAGCAGCGAGGACGAGGAAGACAGTGGGAAGGGGGAACCCACAGCTAAAGGCTCTAGAAAGATGGCCAGACTGGGCAGCACCAGTGGTGAGGAAAGTGACTTGGAGAGGGAGGTAAGTGACAGCGAGGCAGGGGGAGGCCCCCAGGGGGAGAGGAAGAACCGCTCTTCCAAGAAGAGCTCCAGGAAAGGCAGGACACGAAGCTCCTCTTCCTCCTCAGATGGAAGTCCAGAGGCCAAAGGAGGGAAGGCTGGCTCAGGTCGCCGTGGAGAGGACCACCCGGCTGTGATGAGGCTGAAGCGCTACATTCGGGCCTGTGGTGCCCATCGAAACTACAAGAAGCTGTTGGGCTCCTGTTGCTCACACAAGGAGCGCCTGAGTATCCTCCGGGCAGAACTGGAAGCGCTAGGCATGAAGGGTACCCCTTCCCTAGGGAAGTGTCGGGCCCTGAAGGAGCAGAGGGAGGAGGCAGCTGAGGTGGCCTCCTTGGATGTTGCGAACATCATCAGTGGCTCGGGCCGGCCACGCAGACGTACAGCCTGGAACCCTTTAGGAGAAGCAGCACCCCCAGGGGAGCTGTACCGACGGACCCTGGACTCAGATGAAGAGCGGCCCCGTCCCGCACCCCCAGACTGGTCACATATGCGTGGCATCATCAGCAGTGATGGCGAGAGTAACTGAGCTCTGCCACCCCCAGGAGGGACCCTTGATACATGTACAAAGCATACATAGCACCCCTTGCCCTGTGTCTGTGGAACAGAAGCAGCTTCCTTCAGAGAAGACTGCAGCTCCCAAGGACACAAGCTGTTGGGATGCTACTTCTCAGCTTCACGCTGTCCCTTTAAGGTGTTTATTTTTTAAGACTCAATAAAGGAGTGTTTTTAATCACCTCATCAAATTTGGTCCCCCATTCTCACCTCCTGTATTTTGGGCCAGGAAACTGAGCAGTAGTCACTGCCTCCACCTCCTCCCCTGGCCTGGTTCCCTTTAATTTCCCCCGGGTTCCTGGAAGAAGTCCCTGCCTCCAGACCCTGTCATCCAACAGCCACCAGACCCTTTTGGAGAAGGGTGTGTGGCTCCTGTGCTGCCCGCCTACCCCGTGGCCCCTCTGCTTTTAGCCTAGTCTGATAACCTAATGCCCACTTGGGAGAGGGATAGAATGACTTGAGGGCAGCCAGTGCTTAAGCCTTCTCCCTTATGCAAACAGCCACTTTGTCCATGGGCTGTTAGCCTCAAAGGGGTGGGGAAAAGCCCATACCTCCTGGGCCAGTCCTAGCCCTCTAGGCCTCTGGCTACAGGCCCAGCCTCTGCAGTCACATGAGGTCTCCACTGAACTCTGGCTGCTGAGGCTTGCGGGAAGATTCGTGAGCATGGAGCTGCCTGGGGTCTGTGTGGGAGGCAAACCTAAGAATCTTTGAAGTCAAAGCAAAGAAAACGAATTAGAGGTCAAGGGGTTGAAGACCACCTTTGAGATCCGAGATCTGGTCACACCTAAAGTCATTAAAATCACTGAAATGTTTAGATACACAGCCCAATAAATTCTCTTTATAAAACACAAGCAGTACTAAAAAAAAAAAAAAAAAA-3' Human-derived HIRIP3 cDNA (SEQ ID NO: 1)
5'-GTAGCAGCGACGCGGTGACGCCACAAAAATGGCGGACGCTGGAAAGCGCCGTTCCTGACTCTAATGTACTTAGACACTTGAAGCCACAAAAGGATTTATCCCCGAGGTTCCTCATCTGCTCGCGAGGATGCCTTTTCTCTTCTGCCTTGCGAAATAACAGCAGCCTAGCTGTTGCCCGTGACCAGTGAGAAAGGCAGCGTCGCGGGCTGATTAGGTTTCACCCAAAGGGTGCCGGCGCCGAATTGGTTTCTAACGAGAACTTTTAAAATGATCCGTTCCAAAAAAGGGTAGGAGCCGCGAGACCCTCCAACTGCCCAGAGAAAACAAGTCTCGTCTGGCAAAGTTCTCGGCCCACGCGGTCCGCGGCCAAGGGCCAACGGTCCCTCGCCCCACGTTGCCGCAGCACTGCGCGTGCGCGAGCCGCTGTCAAACGCGCTGACGGAGGCCGAGAAGAAAAAAAGGCGGGAGCCGTCAATCCCGGGTTGAGCAAA ATGGCGCGGGAGAAGGAGATGCAGGAGTTCACCCGTAGCTTCTTCCGAGGCCGCCCGGACCTCAGCACGCTTACGCATTCCATCGTGCGGCGGAGGTACTTAGCTCACTCGGGCCGCAGCCACCTGGAGCCCGAGGAGAAGCAGGCACTGAAGCGGCTGGTGGAGGAGGAGCTGCTGAAGATGCAGGTGGATGAAGCCGCTTCCAGGGAAGACAAACTGGACCTTACCAAGAAGGGCAAGAGGCCTCCCACCCCTTGTAGCGACCCGGAGAGAAAAAGGTTCCGCTTCAATTCAGAGTCGGAGTCCGGCTCTGAAGCCTCCAGCCCAGACTACTTTGGACCCCCAGCAAAGAATGGGGTGGCAGCAGAAGTCAGCCCAGCCAAAGAGGAGAATCCAAGGCGAGCCTCAAAGGCAGTTGAGGAGAGCAGTGATGAGGAACGGCAGAGGGACCTGCCCGCACAGAGGGGAGAGGAGAGCAGTGAGGAGGAGGAAAAGGGGTACAAGGGGAAGACTAGGAAGAAACCTGTGGTAAAGAAGCAGGCACCAGGCAAGGCCTCAGTCAGTAGGAAGCAGGCCAGGGAAGAAAGTGAGGAGAGCGAGGCAGAACCCGTTCAGAGGACAGCAAAGAAGGTGGAGGGAAATAAAGGAACTAAAAGCCTGAAGGAAAGTGAACAGGAGAGTGAAGAGGAGATCCTAGCCCAGAAGAAAGAGCAGAGAGAGGAGGAAGTGGAGGAGGAAGAGAAAGAAGAGGATGAGGAAAAGGGGGATTGGAAACCCAGAACCAGGAGCAATGGCCGGAGAAAGTCAGCTAGGGAGGAGAGGAGCTGTAAGCAGAAAAGCCAGGCAAAGAGGCTCTTGGGAGACTCAGACAGCGAGGAAGAGCAGAAAGAGGCAGCCAGCAGTGGGGATGACAGTGGGAGAGATAGAGAACCCCCAGTGCAGAGGAAGAGTGAGGACAGGACCCAGCTTAAGGGTGGGAAGAGGTTGAGTGGAAGCAGCGAGGACGAGGAAGACAGTGGGAAGGGGGAACCCACAGCTAAAGGCTCTAGAAAGATGGCCAGACTGGGCAGCACCAGTGGTGAGGAAAGTGACTTGGAGAGGGAGGTAAGTGACAGCGAGGCAGGGGGAGGCCCCCAGGGGGAGAGGAAGAACCGCTCTTCCAAGAAGAGCTCCAGGAAAGGCAGGACACGAAGCTCCTCTTCCTCCTCAGATGGAAGTCCAGAGGCCAAAGGAGGGAAGGCTGGCTCAGGTCGCCGTGGAGAGGACCACCCGGCTGTGATGAGGCTGAAGCGCTACATTCGGGCCTGTGGTGCCCATCGAAACTACAAGAAGCTGTTGGGCTCCTGTTGCTCACACAAGGAGCGCCTGAGTATCCTCCGGGCAGAACTGGAAGCGCTAGGCATGAAGGGTACCCCTTCCCTAGGGAAGTGTCGGGCCCTGAAGGAGCAGAGGGAGGAGGCAGCTGAGGTGGCCTCCTTGGATGTTGCGAACATCATCAGTGGCTCGGGCCGGCCACGCAGACGTACAGCCTGGAACCCTTTAGGAGAAGCAGCACCCCCAGGGGAGCTGTACCGACGGACCCTGGACTCAGATGAAGAGCGGCCCCGTCCCGCACCCCCAGACTGGTCACATATGCGTGGCATCATCAGCAGTGATGGCGAGAGTAACTGA -3'
ヒト由来ＨＩＲＩＰ３　タンパク質（配列番号２）
MAREKEMQEFTRSFFRGRPDLSTLTHSIVRRRYLAHSGRSHLEPEEKQALKRLVEEELLKMQVDEAASREDKLDLTKKGKRPPTPCSDPERKRFRFNSESESGSEASSPDYFGPPAKNGVAAEVSPAKEENPRRASKAVEESSDEERQRDLPAQRGEESSEEEEKGYKGKTRKKPVVKKQAPGKASVSRKQAREESEESEAEPVQRTAKKVEGNKGTKSLKESEQESEEEILAQKKEQREEEVEEEEKEEDEEKGDWKPRTRSNGRRKSAREERSCKQKSQAKRLLGDSDSEEEQKEAASSGDDSGRDREPPVQRKSEDRTQLKGGKRLSGSSEDEEDSGKGEPTAKGSRKMARLGSTSGEESDLEREVSDSEAGGGPQGERKNRSSKKSSRKGRTRSSSSSSDGSPEAKGGKAGSGRRGEDHPAVMRLKRYIRACGAHRNYKKLLGSCCSHKERLSILRAELEALGMKGTPSLGKCRALKEQREEAAEVASLDVANIISGSGRPRRRTAWNPLGEAAPPGELYRRTLDSDEERPRPAPPDWSHMRGIISSDGESN Human-derived HIRIP3 protein (SEQ ID NO: 2)
MAREKEMQEFTRSFFRGRPDLSTLTHSIVRRRYLAHSGRSHLEPEEKQALKRLVEEELLKMQVDEAASREDKLDLTKKGKRPPTPCSDPERKRFRFNSESESGSEASSPDYFGPPAKNGVAAEVSPAKEENPRRASKAVEESSDEERQRDLPAQRGEESSEEEEKGYKGKTRKKPVVKKQAPGKASVSRKQAREESEESEAEPVQRTAKKVEGNKGTKSLKESEQESEEEILAQKKEQREEEVEEEEKEEDEEKGDWKPRTRSNGRRKSAREERSCKQKSQAKRLLGDSDSEEEQKEAASSGDDSGRDREPPVQRKSEDRTQLKGGKRLSGSSEDEEDSGKGEPTAKGSRKMARLGSTSGEESDLEREVSDSEAGGGPQGERKNRSSKKSSRKGRTRSSSSSSDGSPEAKGGKAGSGRRGEDHPAVMRLKRYIRACGAHRNYKKLLGSCCSHKERLSILRAELEALGMKGTPSLGKCRALKEQREEAAEVASLDVANIISGSGRPRRRTAWNPLGEAAPPGELYRRTLDSDEERPRPAPPDWSHMRGIISSDGESN
　ヒト由来ＦＮＤＣ１１は、ｃＤＮＡとして、例えば、ＮＣＢＩアクセッション番号NM_024059.3で登録されている下記の塩基配列（配列番号３）における下線部（93－1049番目）の領域（終始コドン含む）、タンパク質として、例えば、ＮＣＢＩアクセッション番号NP_076964.1で登録されている下記のアミノ酸配列（配列番号４）があげられる。配列番号３の塩基配列は、配列番号４のアミノ酸配列をコードする配列である。 Human-derived FNDC11 is used as a cDNA, for example, as a protein in the underlined region (93-1049) in the following nucleotide sequence (SEQ ID NO: 3) registered in NCBI Accession No. NM_024059.3 (including stop codons). For example, the following amino acid sequence (SEQ ID NO: 4) registered under NCBI accession number NP_076964.1 can be mentioned. The base sequence of SEQ ID NO: 3 is a sequence encoding the amino acid sequence of SEQ ID NO: 4.
ヒト由来ＦＮＤＣ１１　ｃＤＮＡ（配列番号３）
5'-GGAAGAGGCCCCAGCACTGACCTCCGTGGGGGTGGAGATGAGGAGGATGGAAAGGGTGTCTTCCTCCAGCATCTTCCTGAAGCTCCCGGATAATGAGCACCCATGTGGCAGGCCTGGGCCTGGACAAGATGAAGCTGGGCAATCCCCAGTCCTTCCTGGACCAGGAGGAGGCAGATGACCAGCAGCTGCTGGAACCAGAGGCGTGGAAGACCTACACCGAGCGCCGCAATGCCCTGCGTGAGTTCCTGACCTCGGACCTGAGTCCGCACCTGCTCAAGCGCCACCACGCCCGCATGCAGCTGCTGCGTAAGTGCTCCTACTACATCGAGGTCCTGCCCAAGCACCTGGCCCTGGGCGACCAGAACCCGCTGGTGCTGCCTAGCGCCTTGTTCCAGCTCATCGACCCCTGGAAGTTCCAGCGCATGAAGAAGGTGGGCACAGCTCAGACCAAGATCCAGCTCCTGCTGCTCGGGGACCTGTTGGAACAGCTCGACCATGGCCGTGCTGAGCTGGATGCCCTGCTCCGGTCGCCAGACCCACGGCCCTTCCTGGCCGACTGGGCGCTGGTGGAGCGGCGGCTGGCGGACGTGTCGGCCGTCATGGACAGCTTCCTGACCATGATGGTGCCGGGGCGGCTACACGTCAAGCACCGCCTGGTGTCTGATGTCAGTGCCACCAAGATCCCGCACATCTGGCTCATGCTGAGCACCAAGATGCCTGTCGTGTTTGACCGAAAGGCGTCGGCGGCTCACCAGGACTGGGCCCGGCTGCGCTGGTTCGTCACCATCCAGCCAGCCACATCGGAGCAGTATGAGTTGCGCTTCAGGCTGCTGGACCCGCGGACACAGCAGGAGTGCGCCCAGTGTGGCGTCATCCCCGTGGCTGCCTGCACCTTCGACGTCCGAAACCTGCTGCCCAACCGATCCTATAAGTTCACCATCAAGAGGGCCGAGACCTCCACGCTGGTGTACGAGCCCTGGAGGGACAGCCTCACCCTGCACACCAAGCCGGAGCCCCTGGAGGGGCCCGCCCTCAGCCACTCTGTCTGAGAGATGATTTTCTAATATTTATCCACTAATAAAGAAGAGTGTAAATGCACATATGGAATTAAAGAAGCAAACCTATTTATGTTTTAAAAAAAAAAAAAAAAAA-3' Human-derived FNDC11 cDNA (SEQ ID NO: 3)
5'-GGAAGAGGCCCCAGCACTGACCTCCGTGGGGGTGGAGATGAGGAGGATGGAAAGGGTGTCTTCCTCCAGCATCTTCCTGAAGCTCCCGGATA ATGAGCACCCATGTGGCAGGCCTGGGCCTGGACAAGATGAAGCTGGGCAATCCCCAGTCCTTCCTGGACCAGGAGGAGGCAGATGACCAGCAGCTGCTGGAACCAGAGGCGTGGAAGACCTACACCGAGCGCCGCAATGCCCTGCGTGAGTTCCTGACCTCGGACCTGAGTCCGCACCTGCTCAAGCGCCACCACGCCCGCATGCAGCTGCTGCGTAAGTGCTCCTACTACATCGAGGTCCTGCCCAAGCACCTGGCCCTGGGCGACCAGAACCCGCTGGTGCTGCCTAGCGCCTTGTTCCAGCTCATCGACCCCTGGAAGTTCCAGCGCATGAAGAAGGTGGGCACAGCTCAGACCAAGATCCAGCTCCTGCTGCTCGGGGACCTGTTGGAACAGCTCGACCATGGCCGTGCTGAGCTGGATGCCCTGCTCCGGTCGCCAGACCCACGGCCCTTCCTGGCCGACTGGGCGCTGGTGGAGCGGCGGCTGGCGGACGTGTCGGCCGTCATGGACAGCTTCCTGACCATGATGGTGCCGGGGCGGCTACACGTCAAGCACCGCCTGGTGTCTGATGTCAGTGCCACCAAGATCCCGCACATCTGGCTCATGCTGAGCACCAAGATGCCTGTCGTGTTTGACCGAAAGGCGTCGGCGGCTCACCAGGACTGGGCCCGGCTGCGCTGGTTCGTCACCATCCAGCCAGCCACATCGGAGCAGTATGAGTTGCGCTTCAGGCTGCTGGACCCGCGGACACAGCAGGAGTGCGCCCAGTGTGGCGTCATCCCCGTGGCTGCCTGCACCTTCGACGTCCGAAACCTGCTGCCCAACCGATCCTATAAGTTCACCATCAAGAGGGCCGAGACCTCCACGCTGGTGTACGAGCCCTGGAGGGACAGCCTCACCCTGCACACCAAGCCGGAGCCCCTGGAGGGGCCCGCCCTCAGCCACTCTGTCTGA GAGATGATTTTCTAATATTTATCCACTAATAAAGAAGAGTGTAAATGCACATATGGAATTAAAGAAGCAAACCTATTTATGTTTAAAAAAAAAAAAAAAAA-3'
ヒト由来ＦＮＤＣ１１　タンパク質（配列番号４）
MSTHVAGLGLDKMKLGNPQSFLDQEEADDQQLLEPEAWKTYTERRNALREFLTSDLSPHLLKRHHARMQLLRKCSYYIEVLPKHLALGDQNPLVLPSALFQLIDPWKFQRMKKVGTAQTKIQLLLLGDLLEQLDHGRAELDALLRSPDPRPFLADWALVERRLADVSAVMDSFLTMMVPGRLHVKHRLVSDVSATKIPHIWLMLSTKMPVVFDRKASAAHQDWARLRWFVTIQPATSEQYELRFRLLDPRTQQECAQCGVIPVAACTFDVRNLLPNRSYKFTIKRAETSTLVYEPWRDSLTLHTKPEPLEGPALSHSV Human-derived FNDC11 protein (SEQ ID NO: 4)
MSTHVAGLGLDKMKLGNPQSFLDQEEADDQQLLEPEAWKTYTERRNALREFLTSDLSPHLLKRHHARMQLLRKCSYYIEVLPKHLALGDQNPLVLPSALFQLIDPWKFQRMKKVGTAQTKIQLLLLGDLLEQLDHGRAELDALLRSPDPRPFLADWALVERRLADVSAVMDSFLTMMVPGRLHVKHRLVSDVSATKIPHIWLMLSTKMPVVFDRKASAAHQDWARLRWFVTIQPATSEQYELRFRLLDPRTQQECAQCGVIPVAACTFDVRNLLPNRSYKFTIKRAETSTLVYEPWRDSLTLHTKPEPLEGPALSHSV
　ヒト由来ＳＬＣ１Ａ３は、ｃＤＮＡとして、例えば、ＮＣＢＩアクセッション番号NM_004172.5で登録されている下記の塩基配列（配列番号５）における下線部（226－1854番目）の領域（終始コドン含む）、タンパク質として、例えば、ＮＣＢＩアクセッション番号NP_004163.3で登録されている下記のアミノ酸配列（配列番号６）があげられる。配列番号５の塩基配列は、配列番号６のアミノ酸配列をコードする配列である。 Human-derived SLC1A3 is used as a cDNA, for example, as a protein in the underlined portion (226-1854) region (including stop codon) in the following nucleotide sequence (SEQ ID NO: 5) registered at NCBI Accession No. NM_004172.5. For example, the following amino acid sequence (SEQ ID NO: 6) registered under NCBI accession number NP_004163.3. The base sequence of SEQ ID NO: 5 is a sequence encoding the amino acid sequence of SEQ ID NO: 6.
ヒト由来ＳＬＣ１Ａ３　ｃＤＮＡ（配列番号５）
5'-AGAGCACATGCACACTGTCAGGGCTAGCCTGCCTGCTTACGCGCGCTGCGGATTGTTGCTCCGTTGTACCTGCTGGGGAATTCACCTCGTTACTGCTTGATATCTTCCACCCCTTACAAAATCAGAAAAGTTGTGTTTTCTAATACCAAAGAGGAGGTTTGGCTTTCTGTGGGTGATTCCCAGACACTGAAGTGCAAAGAAGAGACCCTCCTAGAAAAGTAAAATATGACTAAAAGCAATGGAGAAGAGCCCAAGATGGGGGGCAGGATGGAGAGATTCCAGCAGGGAGTCCGTAAACGCACACTTTTGGCCAAGAAGAAAGTGCAGAACATTACAAAGGAGGATGTTAAAAGTTACCTGTTTCGGAATGCTTTTGTGCTGCTCACAGTCACCGCTGTCATTGTGGGTACAATCCTTGGATTTACCCTCCGACCATACAGAATGAGCTACCGGGAAGTCAAGTACTTCTCCTTTCCTGGGGAACTTCTGATGAGGATGTTACAGATGCTGGTCTTACCACTTATCATCTCCAGTCTTGTCACAGGAATGGCGGCGCTAGATAGTAAGGCATCAGGGAAGATGGGAATGCGAGCTGTAGTCTATTATATGACTACCACCATCATTGCTGTGGTGATTGGCATAATCATTGTCATCATCATCCATCCTGGGAAGGGCACAAAGGAAAACATGCACAGAGAAGGCAAAATTGTACGAGTGACAGCTGCAGATGCCTTCCTGGACTTGATCAGGAACATGTTCCCTCCAAATCTGGTAGAAGCCTGCTTTAAACAGTTTAAAACCAACTATGAGAAGAGAAGCTTTAAAGTGCCCATCCAGGCCAACGAAACGCTTGTGGGTGCTGTGATAAACAATGTGTCTGAGGCCATGGAGACTCTTACCCGAATCACAGAGGAGCTGGTCCCAGTTCCAGGATCTGTGAATGGAGTCAATGCCCTGGGTCTAGTTGTCTTCTCCATGTGCTTCGGTTTTGTGATTGGAAACATGAAGGAACAGGGGCAGGCCCTGAGAGAGTTCTTTGATTCTCTTAACGAAGCCATCATGAGACTGGTAGCAGTAATAATGTGGTATGCCCCCGTGGGTATTCTCTTCCTGATTGCTGGGAAGATTGTGGAGATGGAAGACATGGGTGTGATTGGGGGGCAGCTTGCCATGTACACCGTGACTGTCATTGTTGGCTTACTCATTCACGCAGTCATCGTCTTGCCACTCCTCTACTTCTTGGTAACACGGAAAAACCCTTGGGTTTTTATTGGAGGGTTGCTGCAAGCACTCATCACCGCTCTGGGGACCTCTTCAAGTTCTGCCACCCTACCCATCACCTTCAAGTGCCTGGAAGAGAACAATGGCGTGGACAAGCGCGTCACCAGATTCGTGCTCCCCGTAGGAGCCACCATTAACATGGATGGGACTGCCCTCTATGAGGCTTTGGCTGCCATTTTCATTGCTCAAGTTAACAACTTTGAACTGAACTTCGGACAAATTATTACAATCAGCATCACAGCCACAGCTGCCAGTATTGGGGCAGCTGGAATTCCTCAGGCGGGCCTGGTCACTATGGTCATTGTGCTGACATCTGTCGGCCTGCCCACTGACGACATCACGCTCATCATCGCGGTGGACTGGTTCCTGGATCGCCTCCGGACCACCACCAACGTACTGGGAGACTCCCTGGGAGCTGGGATTGTGGAGCACTTGTCACGACATGAACTGAAGAACAGAGATGTTGAAATGGGTAACTCAGTGATTGAAGAGAATGAAATGAAGAAACCATATCAACTGATTGCACAGGACAATGAAACTGAGAAACCCATCGACAGTGAAACCAAGATGTAGACTAACATAAAGAAACACTTTCTTGAGCACCAGGTGTTAAAAACCATTATAAAATCTTTCCATCTCATTACAGCTCATTCGCTCCAGCAAGCCCGTCATCTTCCCTTTCCTCCCTTCTGATAAGACTGGAAAATAGTCCTCCAAAACACAAGGGAGGATTTTGGGTGGCCAAAGTGTACAATTTTCATCCCACAATTGAAATTTTTAAATCATTTCATGTTAGTCTTACCGAATAAGGTACCAAGATCACAAATAGTGTTGATCAGATCTTACAAGTTTATGTGGCACACAATCCTATAAATGTGATTTTTTTATATAAGTTAAAGAGACAAATAGTAGGCTAAAAACATTTTAAAATCAACTTTTGAAATTTAAAAATCTTTCAGAATACAATTCAGTTTTAGTTTCAAAATGTTAACAACTTGAATTACAACCGGTTATCAGTTGGACAGTAAGATTTTATCCCTTTCTCTTCTGACTGGTATACCTATTTCATTAGTAGCTAGGTGCACATATACATCTAGCACAGCTGTGAGGACAGACAGAAGGCAAAGTTTCCATGTGGCCTTGAGCAAGTCCCATCTCACCTCTAGGCCTCAGTGTCCTCATCTATAAAATGAGGGACTTCCCTAGAAGTCTTCATGGTCTCTTCCAGCCCAGACATCCTGTGATGTCATGAAAGCACCTGCCCTCTGTTTCCCCTCAGAACACCCTGTACCATCCATGGAGCACGAGGCCTTCAGAAAAGACACTTCAATGGGAGTGAACATTTCTAACTAAGGACAGGATGGCTGTGTGTGGTGGTCACCAGGTCCTGTGAGCAAAGTGCAGGTTATGCAAGTCGCCAGGCAGGAGGCCATTCCAGGAGTGGGATTATTCATCAAACTCTTTGCCCAGTTCATCCCAATGGGGGAAGTATTCCCTTCTTTCCTACTCTGGGAAGAATGTCTCCTGCCACTCCTCAACTGATGATAGACTTCGAAAACAGATGAGAAGACTAGCAGCTAGCAAGGGTGCTTGTGGTCACACTGTGGAACACTAAAGAGCTAGGAAAGAGTTGAGCACAGGCAACATTACAAACAAAGGATTTGAAAACACCAAGAGTACAGGTCTTCTTTAAGGAAGAATAAAAAAGAAGAGGTTCATTTTTCTGGCTTTTTTTTTCACCTGAAACACTTTTTCTCGAGTCCAAAATCATTCCCCCCGTGAAGTCTGCTTACCAAAACATAAGACGACTTATATATTTGAAAGAAGTCAAATGAATGAGCTCTCTAATAGAAGTCCATGAGTTGAGTGGGTATTTCTTATTTGAAAGTGTTTTTCTTTAATCAAAAGTCCTTAGAATGAGGGAAACAAAATATTTATTTGTTTTGGAATCCCACTTATCAAATCATTCAAAACTTTCAGCTGGAGTGGGGTTTGCTTTTGTTTTGTTTGTGTCCATAAGAGAAATGGTAGAAGATGAATCAGTATGAAGACACTGTCAATGAGGTTATGAGAAAAAAACAGCAGGGGCATTAGTTTCAGGCAAGGCAGCTCCCAGGTTTAGAGATTAATTTTTACCCCCTAAGGAATATCCAGTCAAAGACGCTGAGTGGGAGCTGTCAGGCAGTAGCAGCTGTGTTTGAGTTTCTGGCTGAAAATGGTGAAGAATGGACTTAATTATGCTAACAAACTGAAAAATCTAGACATAGATCCTCTGATATACAATTAGAGATATTTTTATATAGACCCCAAGCATTCTGTGCATAAAAGTTAACATTAGGCTGTGGTGCAGTAACCATTTAATGTCGAGGCTCTATTTCGGAAATACACTACAAATGTTAAAGTACGTGGCTGTCCTCTTAAGACACTAGTAGAGCAAAGACTTAATCATATCAACTTAATTCTGTTACACAATATGTGTTTTTTAATATACTAACCATTTCTTATGGAAAGGTCCTGTGGGGAGCCCATCCTCTCGCCAAGCCATCACAGGCTCTGCATACACATGCACTCAGTGTGGACTGGGAAGCATTACTTTGTAGATGTATTTTCAATAAAGAAAAAAATAGTTTTACATTAA-3' Human-derived SLC1A3 cDNA (SEQ ID NO: 5)
5'-AGAGCACATGCACACTGTCAGGGCTAGCCTGCCTGCTTACGCGCGCTGCGGATTGTTGCTCCGTTGTACCTGCTGGGGAATTCACCTCGTTACTGCTTGATATCTTCCACCCCTTACAAAAATCAGAAAAGTTGTGTTTTCTAATACCAAAGGAGGTTTGGCTTTCTAATACCAAAGGAGGTTTGGCTTTCTGGGTAGA. ATGACTAAAAGCAATGGAGAAGAGCCCAAGATGGGGGGCAGGATGGAGAGATTCCAGCAGGGAGTCCGTAAACGCACACTTTTGGCCAAGAAGAAAGTGCAGAACATTACAAAGGAGGATGTTAAAAGTTACCTGTTTCGGAATGCTTTTGTGCTGCTCACAGTCACCGCTGTCATTGTGGGTACAATCCTTGGATTTACCCTCCGACCATACAGAATGAGCTACCGGGAAGTCAAGTACTTCTCCTTTCCTGGGGAACTTCTGATGAGGATGTTACAGATGCTGGTCTTACCACTTATCATCTCCAGTCTTGTCACAGGAATGGCGGCGCTAGATAGTAAGGCATCAGGGAAGATGGGAATGCGAGCTGTAGTCTATTATATGACTACCACCATCATTGCTGTGGTGATTGGCATAATCATTGTCATCATCATCCATCCTGGGAAGGGCACAAAGGAAAACATGCACAGAGAAGGCAAAATTGTACGAGTGACAGCTGCAGATGCCTTCCTGGACTTGATCAGGAACATGTTCCCTCCAAATCTGGTAGAAGCCTGCTTTAAACAGTTTAAAACCAACTATGAGAAGAGAAGCTTTAAAGTGCCCATCCAGGCCAACGAAACGCTTGTGGGTGCTGTGATAAACAATGTGTCTGAGGCCATGGAGACTCTTACCCGAATCACAGAGGAGCTGGTCCCAGTTCCAGGATCTGTGAATGGAGTCAATGCCCTGGGTCTAGTTGTCTTCTCCATGTGCTTCGGTTTTGTGATTGGAAACATGAAGGAACAGGGGCAGGCCCTGAGAGAGTTCTTTGATTCTCTTAACGAAGCCATCATGAGACTGGTAGCAGTAATAATGTGGTATGCCCCCGTGGGTATTCTCTTCCTGATTGCTGGGAAGATTGTGGAGATGGAAGACATGGGTGTGATTGGGGGGCAGCTTGCCATGTACACCGTGACTGTCATTGTTGGCTTACTCATTCACGCAGTCATCGTCTTGCCACTCCTCTACTTCTTGGTAACACGGAAAAACCCTTGGGTTTTTATTGGAGGGTTGCTGCAAGCACTCATCACCGCTCTGGGGACCTCTTCAAGTTCTGCCACCCTACCCATCACCTTCAAGTGCCTGGAAGAGAACAATGGCGTGGACAAGCGCGTCACCAGATTCGTGCTCCCCGTAGGAGCCACCATTAACATGGATGGGACTGCCCTCTATGAGGCTTTGGCTGCCATTTTCATTGCTCAAGTTAACAACTTTGAACTGAACTTCGGACAAATTATTACAATCAGCATCACAGCCACAGCTGCCAGTATTGGGGCAGCTGGAATTCCTCAGGCGGGCCTGGTCACTATGGTCATTGTGCTGACATCTGTCGGCCTGCCCACTGACGACATCACGCTCATCATCGCGGTGGACTGGTTCCTGGATCGCCTCCGGACCACCACCAACGTACTGGGAGACTCCCTGGGAGCTGGGATTGTGGAGCACTTGTCACGACATGAACTGAAGAACAGAGATGTTGAAATGGGTAACTCAGTGATTGAAGAGAATGAAATGAAGAAACCATATCAACTGATTGCACAGGACAATGAAACTGAGAAACCCATCGACAGTGAAACCAAGATGTAG -3'
ヒト由来ＳＬＣ１Ａ３　タンパク質（配列番号６）
MTKSNGEEPKMGGRMERFQQGVRKRTLLAKKKVQNITKEDVKSYLFRNAFVLLTVTAVIVGTILGFTLRPYRMSYREVKYFSFPGELLMRMLQMLVLPLIISSLVTGMAALDSKASGKMGMRAVVYYMTTTIIAVVIGIIIVIIIHPGKGTKENMHREGKIVRVTAADAFLDLIRNMFPPNLVEACFKQFKTNYEKRSFKVPIQANETLVGAVINNVSEAMETLTRITEELVPVPGSVNGVNALGLVVFSMCFGFVIGNMKEQGQALREFFDSLNEAIMRLVAVIMWYAPVGILFLIAGKIVEMEDMGVIGGQLAMYTVTVIVGLLIHAVIVLPLLYFLVTRKNPWVFIGGLLQALITALGTSSSSATLPITFKCLEENNGVDKRVTRFVLPVGATINMDGTALYEALAAIFIAQVNNFELNFGQIITISITATAASIGAAGIPQAGLVTMVIVLTSVGLPTDDITLIIAVDWFLDRLRTTTNVLGDSLGAGIVEHLSRHELKNRDVEMGNSVIEENEMKKPYQLIAQDNETEKPIDSETKM Human-derived SLC1A3 protein (SEQ ID NO: 6)
MTKSNGEEPKMGGRMERFQQGVRKRTLLAKKKVQNITKEDVKSYLFRNAFVLLTVTAVIVGTILGFTLRPYRMSYREVKYFSFPGELLMRMLQMLVLPLIISSLVTGMAALDSKASGKMGMRAVVYYMTTTIIAVVIGIIIVIIIHPGKGTKENMHREGKIVRVTAADAFLDLIRNMFPPNLVEACFKQFKTNYEKRSFKVPIQANETLVGAVINNVSEAMETLTRITEELVPVPGSVNGVNALGLVVFSMCFGFVIGNMKEQGQALREFFDSLNEAIMRLVAVIMWYAPVGILFLIAGKIVEMEDMGVIGGQLAMYTVTVIVGLLIHAVIVLPLLYFLVTRKNPWVFIGGLLQALITALGTSSSSATLPITFKCLEENNGVDKRVTRFVLPVGATINMDGTALYEALAAIFIAQVNNFELNFGQIITISITATAASIGAAGIPQAGLVTMVIVLTSVGLPTDDITLIIAVDWFLDRLRTTTNVLGDSLGAGIVEHLSRHELKNRDVEMGNSVIEENEMKKPYQLIAQDNETEKPIDSETKM
　ヒト由来ＴＭＥＭ３３は、ｃＤＮＡとして、例えば、ＮＣＢＩアクセッション番号NM_018126.3で登録されている下記の塩基配列（配列番号７）における下線部（57－800番目）の領域（終始コドン含む）、タンパク質として、例えば、ＮＣＢＩアクセッション番号NP_060596.2で登録されている下記のアミノ酸配列（配列番号８）があげられる。配列番号７の塩基配列は、配列番号８のアミノ酸配列をコードする配列である。 Human-derived TMEM33 can be used as a cDNA, for example, as a protein in the underlined region (57-800th) region (including stop codon) in the following nucleotide sequence (SEQ ID NO: 7) registered at NCBI Accession No. NM_018126.3. For example, the following amino acid sequence (SEQ ID NO: 8) registered under NCBI accession number NP_060596.2 can be mentioned. The nucleotide sequence of SEQ ID NO: 7 is a sequence encoding the amino acid sequence of SEQ ID NO: 8.
ヒト由来ＴＭＥＭ３３　ｃＤＮＡ（配列番号７）
5'-CTCCCCTTTCTTCTCTCTTCGCGGTTGCGGCGTCGCAGACGCTAGTGTGAGCCCCCATGGCAGATACGACCCCGAACGGCCCCCAAGGGGCGGGCGCTGTGCAATTCATGATGACCAATAAACTGGACACGGCAATGTGGCTTTCTCGCTTGTTCACAGTTTACTGCTCTGCTCTGTTTGTTCTGCCTCTTCTTGGGTTGCATGAAGCAGCAAGCTTTTACCAACGTGCTTTGCTGGCAAATGCTCTTACCAGTGCTCTGAGGCTGCATCAAAGATTACCACACTTCCAGTTAAGCAGAGCATTCCTGGCCCAGGCTTTGTTAGAGGACAGCTGCCACTACCTGTTGTATTCACTCATCTTTGTAAATTCCTATCCAGTTACAATGAGTATCTTCCCAGTCTTGTTATTCTCTTTGCTTCATGCTGCCACATATACGAAAAAGGTCCTTGACGCAAGGGGCTCAAATAGTTTACCTCTGCTGAGATCTGTCTTGGACAAATTAAGTGCTAATCAACAAAATATTCTGAAATTCATTGCTTGCAATGAAATATTCCTGATGCCTGCGACAGTTTTTATGCTTTTTAGTGGTCAAGGAAGTTTGCTCCAACCTTTTATATACTATAGATTTCTTACCCTTCGATATTCGTCTCGAAGAAACCCATATTGTCGGACCTTATTTAATGAACTGAGGATTGTTGTTGAACACATAATAATGAAACCTGCTTGCCCACTGTTTGTGAGAAGACTTTGTCTCCAGAGCATTGCCTTTATAAGCAGATTGGCACCAACAGTTCCATAGTTTAACATCTAGTTAAGCTACAAATATAGTATAAGCATTATTAGCAGCTGGTACTTCTGCTAGGGGTTGTAAATTCCAGGTGTTACACTGACCTCAATCCAATTTACATAATTTACATAAATGCATCTCGGTGGAAAAATAATCATTTTCTTGGCATGTTAAATCAAGCTTAAAAAGTTTTGAGAAAATTTTACTGCGCTGTGTTGCTAATGGTTAAAGAAGTCTGTATCTAGTGATAAATATACCAGTTTTTTTAAAAAGATGCTGTTGTGCCTATATCATGAAGTACATTAATTTCTCATGTAAAAAAAATAGCTCTAAAATTTGTTTCAACCTAATTGGTAACCTGAGTTTATATCTGGCATGAATTCATTATGGTGATACACATATGTGAATTCAGTACATTTTGAGACAGTATTCTACCATTCAGTAATTTTGGTTAATGATTTTAACACTTCTCAGTGTATTTAATTTCAAATTGTTTTTTTAATTGGTTTTATGCTGCTTTGTTAGGACAGATGTGTTTTGAATGTACCATTATAAGAAGAATTCTATGTATCTTAAACTATGATCTTCTAAAATTTTATTTCCGTAAGTACTTCTGTGGCCTTGAGTATTTTTTAAAAGGCTCAACTGTAAGCCTCTTAGCCAGTTGGATAAATATTTGGGGTCACCTAGCCATTGAAAGCAGAAAGCAGTAGTGACACAGCTTTCCCTTCAAAGAGCCATTGAGAAACATTTCTCAAACAGGAAATCCTTCTTTTACTAATGTGGACATATAGATTATTCGTATTATAGTTTGTAGAACTACCTAGTTCAGAATCTTGACTGCCAGTTTTCTTGGTTTCTTAGGCTTGAATTTTCATAGACAATTGCAACAGTTTAGATGCCTTTTGAAAGGAATGTAATGAAGATTCAGCATCTGACTATATGTGTGTCTATCCTGAAATAATAATGGAGAGTATACTGTAGATTACATGTTTACCCATCAAATCTGACTTAAAAGGTTAAATGGAAGGTTTTATAGGTAAGGTAATTGATTGGGAATGGGGTAGGGGGAGGAGTTGTGGGGGAATAATGTGCATTTCAGTCTCAACGCATAGATAAATTTAGGGGAATTGGATGTATTATTCAACTTTGATTTGGGTTGTAAAATGTGTTAAATCCTGTTCATTGAACTCCCATCAACTCTTATAAAATTCATGCTGATCTTCATTACCGTTGCATGATTGGAAATGTTTAAAACATTGTACAGTTTTAGTATAGAGAAATGTAATGGTTTTTGTGACCAGTTTCTGTCTGCATGTAATTTGGATTTCTCAAATACATTCATTAGTAATTTATCAGTAACATTAGTTTTATTTTTGTTCATCTCCTTATCTATAAAAAGGGGATATTCTTAGGATAAATACATGAAAAATTATACTTGATAGCTTAACTATAATCAGCTATTTTTGTATTTTTGTAATATTTGTCCACTAAGCTGGAGAAGCAGCCTCATACAGTTGATTTTGTGTATGTGGCTAGTCTTATTGTCACTATGTAAGTAATCCAATGGTTTTAGAAACTAAACTTTCTAGAGCAATAAAATGACTATAATGTTAAGTAAACATAATGTTGATTTCTAATTATGTTTTAAAAAATGAAGTCTTGAATTATATCAAGAAATTTTGGCAGCTGAAGTCATGTTTATTTTGAAGCTGTTAGTTTTTTCCTATAATTTAAAAAGATCTTTTAGATTTATAGAAGAGTCAGAAATGTACAAGAGAGTTTTTTTGTTGTTGTTTTTGTTTTTTGAGACAGAGTCTGTCTCTGTCGCCAAGGCTGGAGTGCAGTGGCGCAATCCTGGCTCACTGTAGCCTCTGCCTCCTGGGTTCAAGTGCTTCTCCTGCCTCAGCCTCCCGAGTAGCTGGGACTACAGGTGCACGCCACCACGCCTGTAGTCCCAGCTGTATTGTAAAAATACAAAATTTTAGTATTTTTAGTAGAGACAGGGTTTCACCATGTTGGCCAGGATGGTCTCGATCTCCTGACCTCGTGATCTGCCTGCCTCGGCCTCCCAAAGTGCCGGGATTACAGGTGTGAGCCACCGCGCCCTGCCAAGAAGAGTTCTTTTGCATACCCTTTACTCAGGTCCTCTCATGTTAACGTTTTACATAACTGTAGAACATTTATCTAAAGTAAGATATTAGCCCAGAACAATACTACTAACTGAAGTATAAAACTTATTTGAATTTCAACAGTTTTTTTTTCATTTCTTATTTTCCTTTTGTGTGCTCTGTTTATACCATGATCCATGATTTTTTTAAAATCATGATTGTCTTTTAAAGATCTGTGTGTCTCTGTTTTGAGTTTTTCCTGTTTATTTTGAAAAGTACTGTTGGTCAAGATAATTGGTCAATAATCCATGTTGGTTTTAACAAAAAGCATTTTAACATTAAAAATATTACAGTATAAAATAACACTCTGTGCTTTAAATTGAGGTTTTATGTCATTTTAGCAGAATTATAATATTTCTGATATACTCATGTTTGACAAGTTGAAACAGATTTGTTTCTTAAAGGAAGGTTTAATATACAAAAAAAGGTAATCTTAAACTTACGAAAAAGTAAATTTTACAATTTGAGCATTACTAGATGTTTAGTTTGCATGAACTCATAGTTAGAAATTCTGCAATAGGAATATCTACAACCGGCTGATTTGGAATTTGAAATTATAGTGTTACATGTATACCTATCAAATTAAAATTAAGGAAATACAATAGCAATATATAGAATGAATGTAGTAACAGAAATTAACTCTTTACTGCATCATTGAACTTATTGTTAGTTACAGGTTTAAAAGAAGTTCATTTAACATCCAGTGTGTCTAATTCTTCTGGAAGTGGTGTAGTACCATTGTTCTTCTGGCATTTTTAAATATTAAACCTTTTTGGATAGATGGAAGCCTTATACAAAATCTACTTTATTTTAGCAAGGATTCTCTGTCCTTTTGTATAGTTGGTACCTTACTAATTTAAACTCTAATATCAATCTAAAGAGAAATTTATTATGCAATTTGTATTTAGGTTTTTTTTTTTTTTTTTGGAATGAAGTTCAGAGGTAGATCCTCCTGGAAGAAAGAAAGCAAGCGAACTTTTTAAAGAAAATTAGACTTGAATATTTAAGAATGTCCCTTACAGAGAAAAGGCCAACTATAATACTAAGCTAAAAGTTATGAAAAATTAATAGGTTCTTTTATAGAGCTAAGAATGATGAAACCATCAATACTTCCTTCTTCCTAAAAATCCAGATCAAAACTTCAGGTTAGGTTTCTAAGTTTAGGACATGAATATTATTTTTTTCTGGAAAAGAAGATGAGTATATGTGTAATAAGACAAGTAGAACTGAGAGATTTAGTTTTTTTTTTTTTTAAGTTTTAGTTCAGAATAACATTAATTTTGAGAGATTGAGGTAAAGAACCTTAACTAATGCTAAGGAGTTTATTTTGATTAACATAGGTTATTCTGACCACCACCTCTTCCTTCCTTAATCTCCTTAGAATCTGACAGTCTCAAAGCTGTCACACAAATTAGACTAATTTTGACACTTTGAAATGAAAACTTCAAGGAAGAAGTAGCCACGGACAGTTATGTTTATAATCAGTAGGTGGCACTCTTTCCTCAGGTAGCCCCCCATTTTCACATGATGTGTTTGAAGGTTAAATGCCACCAAAAGTGCTGAGTCAGCTATAAAACTAAGTCCCTGAATTCCATGGCCCTTTTAAATATGTAATCATTCAAGATTGAAAAAAAAAATTAAGCATTTTTTGTTTGTTTGCTTGTTTGTTTTTGAGACGGAGTTTCACTCTTGTTGGCCAGGCTGGAGTGCAATGGCGCCATCTCAGCTCACTGCAACCTCTGCCTCCCGGATTCAAGCAATTCTCCTTCAGCCCTCCAAGTAGCTGGGGTTACAGGTGCCCGCCACCATGCCCAGCTAGTTTTTGTATTTTTAGTAGAGATGAGGTTTCACCATGTTGGCCAGGCTGGTCTTGAACTCCTGACCTCGTGATCCCCCCACCTCGGCCTTCCAAAGTGCTGGATTACAGGCGTGAGCCACTGTGCCTGGCTTGCATTTTTAAAATACTGAATTATTCAAAAGAAGTACCCTGTCAATATGTGCTTTCTAGGAAAACAGTAAAATAGGCCACAATTTGGAGTGACACCATTCAGATCAAGGTCTATCCAGTTTTTTCTTTTCATGCTAAGTGCCTACATCACCGAAACACACTAATATAAAATTATCCTTTCTCCTTCATTTTCAGATGTGTAAAAAATGGTACTTAAAGTGTTTTCATGATCATTTTGTAGGTAGACTAGATATAGCCCGTTGAACCTCTTTTAAAATTTAGACTTTTGATAGTAATATAAAAGCATATTGAAATTTGTAGATATTATATGAGGAATGGCACCTAGATTTGAAAATTATGCTTGGCTTGTAGAGACAACTAGTTTCTCTCGCTCTTTTTTTTTTTTTTTTTTTTTTTTTTGAGACAGATTCTCACTCAGTTGCCCAGGCTGGAGTGCAGTGGTGCAGTCTTGGCTCACTGCAACCTCTGCCTCCTGGGTTAAAGCGATTCTCATGCCTCAGCCTCCCTAGTAGCTGAGACTACAGGCGTGCACCACCACGCCCAGCTAATTTTTGTATTTTTAGTAGAGACAGGATTTCACCATGTTCACCATGTTGGTCAGGCTGGTCTTGAACTCCTGGCCTCAAGTGATCTGCCCGCCTCGACCTCCCAGAGTGCTGGGATTATAGGTGTGAGCCACTAAGCCTGGCTGAGACAACTAGTTTCCCTTAACTCATTGGAATTCTCTAGGATTAGGAGAATTCCACAGAGCCTATATGATATTATAGCTCAACATTTAGTATACCAAAGGCATACCCGTGTAAATCTAGGAGTTATTTCCAGAGATTGTTTTAAGGAGCAGTCTTATATTCAGGGTAGAAAGTTATGATTGGATCTGCTGTTAAGGAGAACAAAGGAGCTTCTAAAGGTTTGGGAGGTTTACTGGTAGTAACTATTCTAGGAAATATTTATGTTTTAAGGTGATGTTCACATGGGTTCTTTAGAAGGAACATAGTCAAGTGTGATGGATTAACTCTATATAGTCTTTCTCCTCTTGTGCGTGTAGGAAATCTGACCTGCAGTGTCAGTTGATGTGACAAGAGATAAAGAAAGCACAGTATTTTAAAATCTAAAGCAGATTCCTTTCTTAGAAAACAATAGGAAAAAATTATAGATGGATGTCTTTGCTGAAATCTAACAATTAGCTCATATTCCATGAGAAAGAGTGGCCTAAGAATTATTTCATGTTACCTAGCCTTCTGAAGCTACTCACTTGATGTGCCTAGCACTTTGAAACTAACCTTTTCTTTCTTTGTTCATGACAGTTTAATTCCAAATATTTACTATTTTCTCTTGTAACTGTTAGAACAGTTCCTTTTGACATTAATTTTTGCCTACATATATATTTTTAAGTTGAGACCAAATCGGTGAAGTGTTGAGCAAGTAACATTTATGATGTGTGTATATTGGAACAAATGTAAAAGGGTTACAAAGATTAGAAACAGAGTCATAAAAAATGGCTTGATTTATAAAGGCATTACTTTTGGTGCTTTATATAATGGCATATATTGAACTAAAAATTTGTATATACAGTATGTCAGCATTTCTTAGTAACTTCTCTTGAATCCATTTTTAATATCTAATATTGTACAGGTTGGGGAGTTACATTCTTCAGGCCAATACTATCCAGACTATATAAATTTATAAAATAAATTGAAAAATTCATTCCCCTGTATTCAAGACCAAAGCACATAAATGCTAATGTAGGGCTCAGAGGGGAAATACAGTTCTCCTGCATATTTGAGAAAATGTGAAGTCCTTTCAAGAAAATCTAATAAACATAATAATCATAGCCTGCTGACACTAAGGAAAAAGGACCTCATTCACTCTTTCTTTTATGCAGTGATTTACTGGTCCCTACTGATTTCCAAATTGGATCACGATAGTAAATTATCCATGCTGGTACCTGTGAAAGTAAGCCCTGGGATCCATATTTGTTTTGTGTTCTGCTTAAATCAGCAAGAATGATAAATTTGATGGTGTGAAATTGGAAGTATCAAGGGCTTTCTTTGGTGATTGAGGGAAATAATGTCTCTACTTGTAATTTATTGTGACCCTTTTTCACTGTATATGCTTTGTATGTCTAATATTTATTTCAATGCAAATTCAATTGTTCCTTCATCTGTATTGTTATATCTAAGATTTTATTGATGTTAAAATCTAATTGTGGAATAAAAATCTCTCTGGAATTTAGCAGATACAAAAATGTTATCTTGCAAAAGAACTAAGAACATTTGTAGTTAGAAATCAGCTTTCCTTTGAGCTTAATTGCCTTTTTGTTAGAATAAGGTGAATTTGAACACACTCCTCTTATCCTCAGCCCATCACAAATAATAGAGATGCCATGATTTTGAGGTCTGATGTGAAACTGGTAAAAATGTGATCTAAGGTGTAACTGGAAAAAAAAAGGAAAGAAAAATTACATTGATGCCTCAGC-3' Human-derived TMEM33 cDNA (SEQ ID NO: 7)
5'-CTCCCCTTTCTTCTCTCTTCGCGGTTGCGGCGTCGCAGACGCTAGTGTGAGCCCCC ATGGCAGATACGACCCCGAACGGCCCCCAAGGGGCGGGCGCTGTGCAATTCATGATGACCAATAAACTGGACACGGCAATGTGGCTTTCTCGCTTGTTCACAGTTTACTGCTCTGCTCTGTTTGTTCTGCCTCTTCTTGGGTTGCATGAAGCAGCAAGCTTTTACCAACGTGCTTTGCTGGCAAATGCTCTTACCAGTGCTCTGAGGCTGCATCAAAGATTACCACACTTCCAGTTAAGCAGAGCATTCCTGGCCCAGGCTTTGTTAGAGGACAGCTGCCACTACCTGTTGTATTCACTCATCTTTGTAAATTCCTATCCAGTTACAATGAGTATCTTCCCAGTCTTGTTATTCTCTTTGCTTCATGCTGCCACATATACGAAAAAGGTCCTTGACGCAAGGGGCTCAAATAGTTTACCTCTGCTGAGATCTGTCTTGGACAAATTAAGTGCTAATCAACAAAATATTCTGAAATTCATTGCTTGCAATGAAATATTCCTGATGCCTGCGACAGTTTTTATGCTTTTTAGTGGTCAAGGAAGTTTGCTCCAACCTTTTATATACTATAGATTTCTTACCCTTCGATATTCGTCTCGAAGAAACCCATATTGTCGGACCTTATTTAATGAACTGAGGATTGTTGTTGAACACATAATAATGAAACCTGCTTGCCCACTGTTTGTGAGAAGACTTTGTCTCCAGAGCATTGCCTTTATAAGCAGATTGGCACCAACAGTTCCATAG -3'
ヒト由来ＴＭＥＭ３３　タンパク質（配列番号８）
MADTTPNGPQGAGAVQFMMTNKLDTAMWLSRLFTVYCSALFVLPLLGLHEAASFYQRALLANALTSALRLHQRLPHFQLSRAFLAQALLEDSCHYLLYSLIFVNSYPVTMSIFPVLLFSLLHAATYTKKVLDARGSNSLPLLRSVLDKLSANQQNILKFIACNEIFLMPATVFMLFSGQGSLLQPFIYYRFLTLRYSSRRNPYCRTLFNELRIVVEHIIMKPACPLFVRRLCLQSIAFISRLAPTVP Human-derived TMEM33 protein (SEQ ID NO: 8)
MADTTPNGPQGAGAVQFMMTNKLDTAMWLSRLFTVYCSALFVLPLLGLHEAASFYQRALLANALTSALRLHQRLPHFQLSRAFLAQALLEDSCHYLLYSLIFVNSYPVTMSIFPVLLFSLLHAATYTKKVLDARGSNSLPLLRSVLDKLSANQNILKVLDARGSNSLPLLRSVLDKLSANQNILKVLDARGSNSLPLLRSVLDKLSANQNILKVLDARGSNSLPLLRSVLDKLSANQNILK
　ヒト由来ＡＢＣＦ１は、ｃＤＮＡとして、例えば、ＮＣＢＩアクセッション番号NM_001025091.2で登録されている下記の塩基配列（配列番号９）における下線部（47－2584番目）の領域（終始コドン含む）、タンパク質として、例えば、ＮＣＢＩアクセッション番号NP_001020262.1で登録されている下記のアミノ酸配列（配列番号１０）があげられる。配列番号９の塩基配列は、配列番号１０のアミノ酸配列をコードする配列である。 Human-derived ABCF1 is used as a cDNA, for example, as a protein in the underlined region (47-2584th) in the following nucleotide sequence (SEQ ID NO: 9) registered in NCBI accession number NM_001025091.2 (including stop codon). For example, the following amino acid sequence (SEQ ID NO: 10) registered under NCBI accession number NP_001020262.1 can be mentioned. The nucleotide sequence of SEQ ID NO: 9 is a sequence encoding the amino acid sequence of SEQ ID NO: 10.
ヒト由来ＡＢＣＦ１　ｃＤＮＡ（配列番号９）
5'-GGAAATAGCACCGGGCGCCGCCACAGTAGCTGTAACTGCCACCGCGATGCCGAAGGCGCCCAAGCAGCAGCCGCCGGAGCCCGAGTGGATCGGGGACGGAGAGAGCACGAGCCCATCAGACAAAGTGGTGAAGAAAGGGAAGAAGGACAAGAAGATCAAAAAAACGTTCTTTGAAGAGCTGGCAGTAGAAGATAAACAGGCTGGGGAAGAAGAGAAAGTGCTCAAGGAGAAGGAGCAGCAGCAGCAGCAACAGCAACAGCAGCAAAAAAAAAAGCGAGATACCCGAAAAGGCAGGCGGAAGAAGGATGTGGATGATGATGGAGAAGAGAAAGAGCTCATGGAGCGTCTTAAGAAGCTCTCAGTGCCAACCAGTGATGAGGAGGATGAAGTACCCGCCCCAAAACCCCGCGGAGGGAAGAAAACCAAGGGTGGTAATGTTTTTGCAGCCCTGATTCAGGATCAGAGTGAGGAAGAGGAGGAGGAAGAAAAACATCCTCCTAAGCCTGCCAAGCCGGAGAAGAATCGGATCAATAAGGCCGTATCTGAGGAACAGCAGCCTGCACTCAAGGGCAAAAAGGGAAAGGAAGAGAAGTCAAAAGGGAAGGCTAAGCCTCAAAATAAATTCGCTGCTCTGGACAATGAAGAGGAGGATAAAGAAGAAGAAATTATAAAGGAAAAGGAGCCTCCCAAACAAGGGAAGGAGAAGGCCAAGAAGGCAGAGCAGGGTTCAGAGGAAGAAGGAGAAGGGGAAGAAGAGGAGGAGGAAGGAGGAGAGTCTAAGGCAGATGATCCCTATGCTCATCTTAGCAAAAAGGAGAAGAAAAAGCTGAAAAAACAGATGGAGTATGAGCGCCAAGTGGCTTCATTAAAAGCAGCCAATGCAGCTGAAAATGACTTCTCCGTGTCCCAGGCGGAGATGTCCTCCCGCCAAGCCATGTTAGAAAATGCATCTGACATCAAGCTGGAGAAGTTCAGCATCTCCGCTCATGGCAAGGAGCTGTTCGTCAATGCAGACCTGTACATTGTAGCCGGCCGCCGCTACGGGCTGGTAGGACCCAATGGCAAGGGCAAGACCACACTCCTCAAGCACATTGCCAACCGAGCCCTGAGCATCCCTCCCAACATTGATGTGTTGCTGTGTGAGCAGGAGGTGGTAGCAGATGAGACACCAGCAGTCCAGGCTGTTCTTCGAGCTGACACCAAGCGATTGAAGCTGCTGGAAGAGGAGCGGCGGCTTCAGGGACAGCTGGAACAAGGGGATGACACAGCTGCTGAGAGGCTAGAGAAGGTGTATGAGGAATTGCGGGCCACTGGGGCGGCAGCTGCAGAGGCCAAAGCACGGCGGATCCTGGCTGGCCTGGGCTTTGACCCTGAAATGCAGAATCGACCCACACAGAAGTTCTCAGGGGGCTGGCGCATGCGTGTCTCCCTGGCCAGGGCACTGTTCATGGAGCCCACACTGCTGATGCTGGATGAGCCCACCAACCACCTGGACCTCAACGCTGTCATCTGGCTTAATAACTACCTCCAGGGCTGGCGGAAGACCTTGCTGATCGTCTCCCATGACCAGGGCTTCTTGGATGATGTCTGCACTGATATCATCCACCTCGATGCCCAGCGGCTCCACTACTATAGGGGCAATTACATGACCTTCAAAAAGATGTACCAGCAGAAGCAGAAAGAACTGCTGAAACAGTATGAGAAGCAAGAGAAAAAGCTGAAGGAGCTGAAGGCAGGCGGGAAGTCCACCAAGCAGGCGGAAAAACAAACGAAGGAAGCCCTGACTCGGAAGCAGCAGAAATGCCGACGGAAAAACCAAGATGAGGAATCCCAGGAGGCCCCTGAGCTCCTGAAGCGCCCTAAGGAGTACACTGTGCGCTTCACTTTTCCAGACCCCCCACCACTCAGCCCTCCAGTGCTGGGTCTGCATGGTGTGACATTCGGCTACCAGGGACAGAAACCACTCTTTAAGAACTTGGATTTTGGCATCGACATGGATTCAAGGATTTGCATTGTGGGCCCTAATGGTGTGGGGAAGAGTACGCTACTCCTGCTGCTGACTGGCAAGCTGACACCGACCCATGGGGAAATGAGAAAGAACCACCGGCTGAAAATTGGCTTCTTCAACCAGCAGTATGCAGAGCAGCTGCGCATGGAGGAGACGCCCACTGAGTACCTGCAGCGGGGCTTCAACCTGCCCTACCAGGATGCCCGCAAGTGCCTGGGCCGCTTCGGCCTGGAGAGTCACGCCCACACCATCCAGATCTGCAAACTCTCTGGTGGTCAGAAGGCGCGAGTTGTGTTTGCTGAGCTGGCCTGTCGGGAACCTGATGTCCTCATCTTGGACGAGCCAACCAATAACCTGGACATAGAGTCTATTGATGCTCTAGGGGAGGCCATCAATGAATACAAGGGTGCTGTGATCGTTGTCAGCCATGATGCCCGACTCATCACAGAAACCAATTGCCAGCTGTGGGTGGTGGAGGAGCAGAGTGTTAGCCAAATCGATGGTGACTTTGAAGACTACAAGCGGGAGGTGTTGGAGGCCCTGGGTGAAGTCATGGTCAGCCGGCCCCGAGAGTGAGCTTTCCTTCCCAGAAGTCTCCCGAGAGACATATTTGTGTGGCCTAGAAGTCCTCTGTGGTCTCCCCTCCTCTGAAGACTGCCTCTGGCCTGCAGCTGACCTGGCAACCATTCAGGCACATGAAGGTGGAGTGTGACCTTGATGTGACCGGGATCCCACTCTGATTGCATCCATTTCTCTGAAAGACTTGTTTGTTCTGCTTCTCTTCATATAACTGAGCTGGCCTTATCCTTGGCATCCCCCTAAACAAACAAGAGGTGACCACCTTATTGTGAGGTTCCATCCAGCCAAGTTTATGTGGCCTATTGTCTCAGGACTCTCATCACTCAGAAGCCTGCCTCTGATTTACCCTACAGCTTCAGGCCCAGCTGCCCCCCAGTCTTTGGGTGGTGCTGTTCTTTTCTGGTGGATTTAATGCTGACTCACTGGTACAAACAGCTGTTGAAGCTCAGAGCTGGAGGTGAGCTTCTGAGGCCTTTGCCATTATCCAGCCCAAGATTTGGTGCCTGCAGCCTCTTGTCTGGTTGAGGACTTGGGGCAGGAAAGGAATGCTGCTGAACTTGAATTTCCCTTTACAAGGGGAAGAAATAAAGGAAAGGAGTTGCTGCCGACCTGTCACTGTTTGGAGATTGATGGGAGTTGGAACTGTTCTCAGTCTTGATTTGCTTTATTCAGTTTTCTAGCAGCTTTTAATAGTCCCCTCTTCCCCACTAAATGGATCTTGTTTGCAGTCTTGCTGACAGTGTTTGCTGTTTAAGGATCATAGGATTCCTTTCCCCCAACCCTTCACGCAAGGAAAAAGCAAAGTGATTCATACCTTC-3' Human-derived ABCF1 cDNA (SEQ ID NO: 9)
5'-GGAAATAGCACCGGGCGCCGCCACAGTAGCTGTAACTGCCACCGCG ATGCCGAAGGCGCCCAAGCAGCAGCCGCCGGAGCCCGAGTGGATCGGGGACGGAGAGAGCACGAGCCCATCAGACAAAGTGGTGAAGAAAGGGAAGAAGGACAAGAAGATCAAAAAAACGTTCTTTGAAGAGCTGGCAGTAGAAGATAAACAGGCTGGGGAAGAAGAGAAAGTGCTCAAGGAGAAGGAGCAGCAGCAGCAGCAACAGCAACAGCAGCAAAAAAAAAAGCGAGATACCCGAAAAGGCAGGCGGAAGAAGGATGTGGATGATGATGGAGAAGAGAAAGAGCTCATGGAGCGTCTTAAGAAGCTCTCAGTGCCAACCAGTGATGAGGAGGATGAAGTACCCGCCCCAAAACCCCGCGGAGGGAAGAAAACCAAGGGTGGTAATGTTTTTGCAGCCCTGATTCAGGATCAGAGTGAGGAAGAGGAGGAGGAAGAAAAACATCCTCCTAAGCCTGCCAAGCCGGAGAAGAATCGGATCAATAAGGCCGTATCTGAGGAACAGCAGCCTGCACTCAAGGGCAAAAAGGGAAAGGAAGAGAAGTCAAAAGGGAAGGCTAAGCCTCAAAATAAATTCGCTGCTCTGGACAATGAAGAGGAGGATAAAGAAGAAGAAATTATAAAGGAAAAGGAGCCTCCCAAACAAGGGAAGGAGAAGGCCAAGAAGGCAGAGCAGGGTTCAGAGGAAGAAGGAGAAGGGGAAGAAGAGGAGGAGGAAGGAGGAGAGTCTAAGGCAGATGATCCCTATGCTCATCTTAGCAAAAAGGAGAAGAAAAAGCTGAAAAAACAGATGGAGTATGAGCGCCAAGTGGCTTCATTAAAAGCAGCCAATGCAGCTGAAAATGACTTCTCCGTGTCCCAGGCGGAGATGTCCTCCCGCCAAGCCATGTTAGAAAATGCATCTGACATCAAGCTGGAGAAGTTCAGCATCTCCGCTCATGGCAAGGAGCTGTTCGTCAATGCAGACCTGTACATTGTAGCCGGCCGCCGCTACGGGCTGGTAGGACCCAATGGCAAGGGCAAGACCACACTCCTCAAGCACATTGCCAACCGAGCCCTGAGCATCCCTCCCAACATTGATGTGTTGCTGTGTGAGCAGGAGGTGGTAGCAGATGAGACACCAGCAGTCCAGGCTGTTCTTCGAGCTGACACCAAGCGATTGAAGCTGCTGGAAGAGGAGCGGCGGCTTCAGGGACAGCTGGAACAAGGGGATGACACAGCTGCTGAGAGGCTAGAGAAGGTGTATGAGGAATTGCGGGCCACTGGGGCGGCAGCTGCAGAGGCCAAAGCACGGCGGATCCTGGCTGGCCTGGGCTTTGACCCTGAAATGCAGAATCGACCCACACAGAAGTTCTCAGGGGGCTGGCGCATGCGTGTCTCCCTGGCCAGGGCACTGTTCATGGAGCCCACACTGCTGATGCTGGATGAGCCCACCAACCACCTGGACCTCAACGCTGTCATCTGGCTTAATAACTACCTCCAGGGCTGGCGGAAGACCTTGCTGATCGTCTCCCATGACCAGGGCTTCTTGGATGATGTCTGCACTGATATCATCCACCTCGATGCCCAGCGGCTCCACTACTATAGGGGCAATTACATGACCTTCAAAAAGATGTACCAGCAGAAGCAGAAAGAACTGCTGAAACAGTATGAGAAGCAAGAGAAAAAGCTGAAGGAGCTGAAGGCAGGCGGGAAGTCCACCAAGCAGGCGGAAAAACAAACGAAGGAAGCCCTGACTCGGAAGCAGCAGAAATGCCGACGGAAAAACCAAGATGAGGAATCCCAGGAGGCCCCTGAGCTCCTGAAGCGCCCTAAGGAGTACACTGTGCGCTTCACTTTTCCAGACCCCCCACCACTCAGCCCTCCAGTGCTGGGTCTGCATGGTGTGACATTCGGCTACCAGGGACAGAAACCACTCTTTAAGAACTTGGATTTTGGCATCGACATGGATTCAAGGATTTGCATTGTGGGCCCTAATGGTGTGGGGAAGAGTACGCTACTCCTGCTGCTGACTGGCAAGCTGACACCGACCCATGGGGAAATGAGAAAGAACCACCGGCTGAAAATTGGCTTCTTCAACCAGCAGTATGCAGAGCAGCTGCGCATGGAGGAGACGCCCACTGAGTACCTGCAGCGGGGCTTCAACCTGCCCTACCAGGATGCCCGCAAGTGCCTGGGCCGCTTCGGCCTGGAGAGTCACGCCCACACCATCCAGATCTGCAAACTCTCTGGTGGTCAGAAGGCGCGAGTTGTGTTTGCTGAGCTGGCCTGTCGGGAACCTGATGTCCTCATCTTGGACGAGCCAACCAATAACCTGGACATAGAGTCTATTGATGCTCTAGGGGAGGCCATCAATGAATACAAGGGTGCTGTGATCGTTGTCAGCCATGATGCCCGACTCATCACAGAAACCAATTGCCAGCTGTGGGTGGTGGAGGAGCAGAGTGTTAGCCAAATCGATGGTGACTTTGAAGACTACAAGCGGGAGGTGTTGGAGGCCCTGGGTGAAGTCATGGTCAGCCGGCCCCGAGAGTGA -3'
ヒト由来ＡＢＣＦ１　タンパク質（配列番号１０）
MPKAPKQQPPEPEWIGDGESTSPSDKVVKKGKKDKKIKKTFFEELAVEDKQAGEEEKVLKEKEQQQQQQQQQQKKKRDTRKGRRKKDVDDDGEEKELMERLKKLSVPTSDEEDEVPAPKPRGGKKTKGGNVFAALIQDQSEEEEEEEKHPPKPAKPEKNRINKAVSEEQQPALKGKKGKEEKSKGKAKPQNKFAALDNEEEDKEEEIIKEKEPPKQGKEKAKKAEQGSEEEGEGEEEEEEGGESKADDPYAHLSKKEKKKLKKQMEYERQVASLKAANAAENDFSVSQAEMSSRQAMLENASDIKLEKFSISAHGKELFVNADLYIVAGRRYGLVGPNGKGKTTLLKHIANRALSIPPNIDVLLCEQEVVADETPAVQAVLRADTKRLKLLEEERRLQGQLEQGDDTAAERLEKVYEELRATGAAAAEAKARRILAGLGFDPEMQNRPTQKFSGGWRMRVSLARALFMEPTLLMLDEPTNHLDLNAVIWLNNYLQGWRKTLLIVSHDQGFLDDVCTDIIHLDAQRLHYYRGNYMTFKKMYQQKQKELLKQYEKQEKKLKELKAGGKSTKQAEKQTKEALTRKQQKCRRKNQDEESQEAPELLKRPKEYTVRFTFPDPPPLSPPVLGLHGVTFGYQGQKPLFKNLDFGIDMDSRICIVGPNGVGKSTLLLLLTGKLTPTHGEMRKNHRLKIGFFNQQYAEQLRMEETPTEYLQRGFNLPYQDARKCLGRFGLESHAHTIQICKLSGGQKARVVFAELACREPDVLILDEPTNNLDIESIDALGEAINEYKGAVIVVSHDARLITETNCQLWVVEEQSVSQIDGDFEDYKREVLEALGEVMVSRPRE Human-derived ABCF1 protein (SEQ ID NO: 10)
MPKAPKQQPPEPEWIGDGESTSPSDKVVKKGKKDKKIKKTFFEELAVEDKQAGEEEKVLKEKEQQQQQQQQQQKKKRDTRKGRRKKDVDDDGEEKELMERLKKLSVPTSDEEDEVPAPKPRGGKKTKGGNVFAALIQDQSEEEEEEEKHPPKPAKPEKNRINKAVSEEQQPALKGKKGKEEKSKGKAKPQNKFAALDNEEEDKEEEIIKEKEPPKQGKEKAKKAEQGSEEEGEGEEEEEEGGESKADDPYAHLSKKEKKKLKKQMEYERQVASLKAANAAENDFSVSQAEMSSRQAMLENASDIKLEKFSISAHGKELFVNADLYIVAGRRYGLVGPNGKGKTTLLKHIANRALSIPPNIDVLLCEQEVVADETPAVQAVLRADTKRLKLLEEERRLQGQLEQGDDTAAERLEKVYEELRATGAAAAEAKARRILAGLGFDPEMQNRPTQKFSGGWRMRVSLARALFMEPTLLMLDEPTNHLDLNAVIWLNNYLQGWRKTLLIVSHDQGFLDDVCTDIIHLDAQRLHYYRGNYMTFKKMYQQKQKELLKQYEKQEKKLKELKAGGKSTKQAEKQTKEALTRKQQKCRRKNQDEESQEAPELLKRPKEYTVRFTFPDPPPLSPPVLGLHGVTFGYQGQKPLFKNLDFGIDMDSRICIVGPNGVGKSTLLLLLTGKLTPTHGEMRKNHRLKIGFFNQQYAEQLRMEETPTEYLQRGFNLPYQDARKCLGRFGLESHAHTIQICKLSGGQKARVVFAELACREPDVLILDEPTNNLDIESIDALGEAINEYKGAVIVVSHDARLITETNCQLWVVEEQSVSQIDGDFEDYKREVLEALGEVMVSRPRE
　ヒト由来ＣＦＤＰ１は、ｃＤＮＡとして、例えば、ＮＣＢＩアクセッション番号NM_006324.3で登録されている下記の塩基配列（配列番号１１）における下線部（152－1051番目）の領域（終始コドン含む）、タンパク質として、例えば、ＮＣＢＩアクセッション番号NP_006315.1で登録されている下記のアミノ酸配列（配列番号１２）があげられる。配列番号１１の塩基配列は、配列番号１２のアミノ酸配列をコードする配列である。 Human-derived CFDP1 can be used as a cDNA, for example, as a protein in the underlined region (152-1051) in the following nucleotide sequence (SEQ ID NO: 11) registered in NCBI Accession No. NM_006324.3 (including stop codons). For example, the following amino acid sequence (SEQ ID NO: 12) registered under NCBI accession number NP_006315.1 can be mentioned. The nucleotide sequence of SEQ ID NO: 11 is a sequence encoding the amino acid sequence of SEQ ID NO: 12.
ヒト由来ＣＦＤＰ１　ｃＤＮＡ（配列番号１１）
5'-GTAGTACTCTCTGCGCATGTGCAAAGCGCTGTCGGGGGCCGCCCTAGCTGCCGTCGCCGCCGCCGGGGCTCTATGGTCTCTCCCTAGAGCTTTGCCGTTGGAGGCGGCTGCTGCGGTCTTGTGAGTTTGACCAGCGTCGAGCGGCAGCAACATGGAGGAATTCGACTCCGAAGACTTCTCTACGTCGGAGGAGGACGAGGACTACGTGCCGTCGGGTGGAGAGTATAGTGAAGATGATGTAAATGAATTAGTGAAGGAAGATGAAGTGGATGGTGAAGAGCAGACACAGAAAACCCAAGGGAAAAAAAGAAAGGCCCAGAGCATTCCAGCCAGGAAGAGAAGACAAGGTGGCCTCTCATTAGAAGAAGAGGAAGAGGAGGATGCCAATTCAGAATCTGAGGGAAGCAGTAGTGAGGAGGAAGATGACGCTGCAGAGCAGGAAAAAGGCATTGGATCAGAGGATGCCAGGAAAAAGAAGGAGGACGAACTCTGGGCCAGCTTCCTCAATGATGTGGGACCAAAATCAAAAGTGCCCCCAAGTACACAAGTTAAGAAAGGAGAGGAGACTGAAGAGACAAGTTCAAGTAAATTGTTGGTAAAAGCAGAAGAGCTAGAGAAACCTAAAGAAACAGAAAAAGTTAAAATCACCAAGGTGTTTGATTTTGCTGGTGAAGAAGTAAGGGTAACTAAGGAAGTGGATGCTACATCTAAAGAGGCCAAATCCTTCTTCAAGCAGAATGAGAAAGAAAAACCACAGGCTAATGTTCCTTCAGCTCTGCCATCACTCCCTGCCGGGTCAGGGTTAAAAAGATCAAGTGGCATGAGCAGCCTTTTGGGGAAAATTGGTGCCAAGAAGCAGAAAATGAGCACCCTTGAGAAGTCCAAACTGGACTGGGAGAGCTTCAAGGAGGAAGAGGGGATTGGTGAAGAACTGGCCATCCATAATCGAGGGAAAGAGGGGTACATTGAACGGAAAGCCTTCCTTGACCGAGTGGATCACAGGCAGTTTGAAATTGAGCGAGATCTCAGGCTGAGCAAAATGAAACCTTGATGTTACGGGCTAAATCAAGAGCAGCTTAATCCTGTTTACAATGTGAGCTTTTTGTGCGTCTGTGAAATGTTTTACAGTGTTTCTCATCATCTGTTTCCCAGCAAGGTCTTTTTTTTTTCTACATTGAAGTTCTGTCTATGTATCTTAATCACAAATGGTTTCATTCACTTTACTTTTAAAAATTTGTCCTTAAATGAATAAATAAAATAAAAGTTGGTCCTGTGAGAGGATAATGAAGATGA-3' Human-derived CFDP1 cDNA (SEQ ID NO: 11)
5'-GTAGTACTCTCTGCGCATGTGCAAAGCGCTGTCGGGGGCCGCCCTAGCTGCCGTCGCCGCCGCCGGGGCTCTATGGTCTCCCTAGAGCTTTGCCGTTGGAGGCGGCTGCTGCGGTCTTGAGTTTGACCAGCGTCGAGCGGCAAC ATGGAGGAATTCGACTCCGAAGACTTCTCTACGTCGGAGGAGGACGAGGACTACGTGCCGTCGGGTGGAGAGTATAGTGAAGATGATGTAAATGAATTAGTGAAGGAAGATGAAGTGGATGGTGAAGAGCAGACACAGAAAACCCAAGGGAAAAAAAGAAAGGCCCAGAGCATTCCAGCCAGGAAGAGAAGACAAGGTGGCCTCTCATTAGAAGAAGAGGAAGAGGAGGATGCCAATTCAGAATCTGAGGGAAGCAGTAGTGAGGAGGAAGATGACGCTGCAGAGCAGGAAAAAGGCATTGGATCAGAGGATGCCAGGAAAAAGAAGGAGGACGAACTCTGGGCCAGCTTCCTCAATGATGTGGGACCAAAATCAAAAGTGCCCCCAAGTACACAAGTTAAGAAAGGAGAGGAGACTGAAGAGACAAGTTCAAGTAAATTGTTGGTAAAAGCAGAAGAGCTAGAGAAACCTAAAGAAACAGAAAAAGTTAAAATCACCAAGGTGTTTGATTTTGCTGGTGAAGAAGTAAGGGTAACTAAGGAAGTGGATGCTACATCTAAAGAGGCCAAATCCTTCTTCAAGCAGAATGAGAAAGAAAAACCACAGGCTAATGTTCCTTCAGCTCTGCCATCACTCCCTGCCGGGTCAGGGTTAAAAAGATCAAGTGGCATGAGCAGCCTTTTGGGGAAAATTGGTGCCAAGAAGCAGAAAATGAGCACCCTTGAGAAGTCCAAACTGGACTGGGAGAGCTTCAAGGAGGAAGAGGGGATTGGTGAAGAACTGGCCATCCATAATCGAGGGAAAGAGGGGTACATTGAACGGAAAGCCTTCCTTGACCGAGTGGATCACAGGCAGTTTGAAATTGAGCGAGATCTCAGGCTGAGCAAAATGAAACCTTGA TGTTACGGGCTAAATCAAGAGCAGCTTAATCCTGTTTACAATGTGAGCTTTTTGTGCGTCTGTGAAATGTTTTACAGTGTTTCTCATCTGTTTCCCAGCAAGGTCTTTTTTTTCTACATTGAAGTTCTGTCTATGTTAATCAAATGGTTTCATTCACTTTACTTAATCAAATGGTTTCATTCACTTT.AATA.
ヒト由来ＣＦＤＰ１　タンパク質（配列番号１２）
MEEFDSEDFSTSEEDEDYVPSGGEYSEDDVNELVKEDEVDGEEQTQKTQGKKRKAQSIPARKRRQGGLSLEEEEEEDANSESEGSSSEEEDDAAEQEKGIGSEDARKKKEDELWASFLNDVGPKSKVPPSTQVKKGEETEETSSSKLLVKAEELEKPKETEKVKITKVFDFAGEEVRVTKEVDATSKEAKSFFKQNEKEKPQANVPSALPSLPAGSGLKRSSGMSSLLGKIGAKKQKMSTLEKSKLDWESFKEEEGIGEELAIHNRGKEGYIERKAFLDRVDHRQFEIERDLRLSKMKP Human-derived CFDP1 protein (SEQ ID NO: 12)
MEEFDSEDFSTSEEDEDYVPSGGEYSEDDVNELVKEDEVDGEEQTQKTQGKKRKAQSIPARKRRQGGLSLEEEEEEDANSESEGSSSEEEDDAAEQEKGIGSEDARKKKEDELWASFLNDVGPKSKVPPSTQVKKGEETEETSSSKLLVKAEELEKPKETEKVKITKVFDFAGEEVRVTKEVDATSKEAKSFFKQNEKEKPQANVPSALPSLPAGSGLKRSSGMSSLLGKIGAKKQKMSTLEKSKLDWESFKEEEGIGEELAIHNRGKEGYIERKAFLDRVDHRQFEIERDLRLSKMKP
　ヒト由来ＰＯＬＲ３ＧＬは、ｃＤＮＡとして、例えば、ＮＣＢＩアクセッション番号NM_032305.3で登録されている下記の塩基配列（配列番号１３）における下線部（121－777番目）の領域（終始コドン含む）、タンパク質として、例えば、ＮＣＢＩアクセッション番号NP_115681.1で登録されている下記のアミノ酸配列（配列番号１４）があげられる。配列番号１３の塩基配列は、配列番号１４のアミノ酸配列をコードする配列である。 Human-derived POLR3GL can be used as a cDNA, for example, as a protein in the underlined region (121-777th) region (including stop codon) in the following nucleotide sequence (SEQ ID NO: 13) registered at NCBI Accession No. NM_032305.3. For example, the following amino acid sequence (SEQ ID NO: 14) registered under NCBI accession number NP_115681.1 can be mentioned. The nucleotide sequence of SEQ ID NO: 13 is a sequence encoding the amino acid sequence of SEQ ID NO: 14.
ヒト由来ＰＯＬＲ３ＧＬ　ｃＤＮＡ（配列番号１３）
5'-AGAACGCCACCGACTTGAGGAAGCCCAGTACATTTCAAGTTGGTCGCGGCTTGGGCTCCGCTTTGGGGAGGGGCAGCAGGTTTATTCACTGGATCTCTGAATACCCAGGCCCCCTCCACCATGGCCAGCCGGGGTGGGGGCCGGGGTCGTGGCCGGGGCCAGTTGACCTTCAACGTGGAGGCCGTGGGCATTGGGAAAGGGGATGCTTTGCCCCCACCCACCCTGCAGCCTTCTCCACTCTTCCCTCCCTTGGAGTTCCGCCCAGTACCTTTGCCCTCAGGCGAGGAAGGGGAATATGTCCTGGCACTGAAGCAAGAGCTACGAGGAGCCATGAGGCAGCTCCCCTACTTCATCCGGCCAGCTGTCCCCAAGAGAGATGTGGAGCGTTATTCAGACAAATATCAGATGTCAGGTCCGATTGACAATGCCATCGATTGGAACCCTGATTGGCGGCGTCTACCCCGGGAGCTAAAGATCCGAGTGCGGAAGCTACAGAAGGAACGGATTACAATTCTGCTCCCCAAGAGGCCCCCTAAGACCACAGAAGATAAGGAGGAAACAATACAGAAACTAGAGACCCTGGAGAAGAAGGAAGAAGAAGTAACTTCAGAGGAGGATGAGGAGAAAGAAGAAGAAGAAGAGAAGGAAGAGGAGGAAGAAGAAGAGTATGATGAAGAAGAACATGAAGAGGAAACTGATTACATCATGTCATATTTTGACAATGGAGAGGACTTTGGTGGTGACAGTGATGACAATATGGACGAGGCTATATACTGAAGAAGGACTCTGGACCCTCGTGTCTTTCTTTAGGATACAGAGAGTAACTGTACCTATTATTTGTTTCTTCAGACAAGCAAATCATTTGGTCAGAGTTCATATAATCTGTCTGTTCCCTGGAGATGGGAATAGAGGATGATGACAGTTTATTTTCTACACTTCCCCTCCTTCCACATTTGTATCACCTTTGCTATCTTGGGGAAAGTGCAAAGGACAAACATCTCAATTGTATGAAGGGAGAAAGGAGAATTGAAAGAAGAACTGGGGTTGTTAGAGCTGAGATGACTGTACACATACCCCTGCCCAATTTATATAGCTCTTTGTGGAGATAATTAGGGGTGGGAGCAGTTTGAAGGAGTAAGCCTGGTTTTATACTTTTAAATAAAGTGTTTTTATCTGTC-3' Human-derived POLR3GL cDNA (SEQ ID NO: 13)
5'-AGAACGCCACCGACTTGAGGAAGCCCAGTACATTTCAAGTTGGTCGCGGCTTGGGCTCCGCTTTGGGGAGGGGCAGCAGGTTTATTCACTGGATCTGTGAATACCCAGGCCCCCTCCACC ATGGCCAGCCGGGGTGGGGGCCGGGGTCGTGGCCGGGGCCAGTTGACCTTCAACGTGGAGGCCGTGGGCATTGGGAAAGGGGATGCTTTGCCCCCACCCACCCTGCAGCCTTCTCCACTCTTCCCTCCCTTGGAGTTCCGCCCAGTACCTTTGCCCTCAGGCGAGGAAGGGGAATATGTCCTGGCACTGAAGCAAGAGCTACGAGGAGCCATGAGGCAGCTCCCCTACTTCATCCGGCCAGCTGTCCCCAAGAGAGATGTGGAGCGTTATTCAGACAAATATCAGATGTCAGGTCCGATTGACAATGCCATCGATTGGAACCCTGATTGGCGGCGTCTACCCCGGGAGCTAAAGATCCGAGTGCGGAAGCTACAGAAGGAACGGATTACAATTCTGCTCCCCAAGAGGCCCCCTAAGACCACAGAAGATAAGGAGGAAACAATACAGAAACTAGAGACCCTGGAGAAGAAGGAAGAAGAAGTAACTTCAGAGGAGGATGAGGAGAAAGAAGAAGAAGAAGAGAAGGAAGAGGAGGAAGAAGAAGAGTATGATGAAGAAGAACATGAAGAGGAAACTGATTACATCATGTCATATTTTGACAATGGAGAGGACTTTGGTGGTGACAGTGATGACAATATGGACGAGGCTATATACTGA AGAAGGACTCTGGACCCTCGTGTCTTTCTTTAGGATACAGAGAGTAACTGTACCTATTATTTGTTTCTTCAGACAAGCAAATCATTTGGTCAGAGTTCATATAATCTGTCTGTTCCCTGGAGATGGGAATAGAGGATGATGACAGTTTATTTTCTACACTTCCCCTCCTTCCACATTTGTATCACCTTTGCTATCTTGGGGAAAGTGCAAAGGACAAACATCTCAATTGTATGAAGGGAGAAAGGAGAATTGAAAGAAGAACTGGGGTTGTTAGAGCTGAGATGACTGTACACATACCCCTGCCCAATTTATATAGCTCTTTGTGGAGATAATTAGGGGTGGGAGCAGTTTGAAGGAGTAAGCCTGGTTTTATACTTTTAAATAAAGTGTTTTTATCTGTC-3 '
ヒト由来ＰＯＬＲ３ＧＬ　タンパク質（配列番号１４）
MASRGGGRGRGRGQLTFNVEAVGIGKGDALPPPTLQPSPLFPPLEFRPVPLPSGEEGEYVLALKQELRGAMRQLPYFIRPAVPKRDVERYSDKYQMSGPIDNAIDWNPDWRRLPRELKIRVRKLQKERITILLPKRPPKTTEDKEETIQKLETLEKKEEEVTSEEDEEKEEEEEKEEEEEEEYDEEEHEEETDYIMSYFDNGEDFGGDSDDNMDEAIY Human-derived POLR3GL protein (SEQ ID NO: 14)
MASRGGGRGRGRGQLTFNVEAVGIGKGDALPPPTLQPSPLFPPLEFRPVPLPSGEEGEYVLALKQELRGAMRQLPYFIRPAVPKRDVERYSDKYQMSGPIDNAIDWNPDWRRLPRELKIRVRKLQKERITILLPKRPPKTTEDKEETIQKLETLEKKEEEVTSEEDEE
　ヒト由来ＣＡＤＭ１は、ｃＤＮＡとして、例えば、ＮＣＢＩアクセッション番号NM_014333.3で登録されている下記の塩基配列（配列番号１５）における下線部（130－1458番目）の領域（終始コドン含む）、タンパク質として、例えば、ＮＣＢＩアクセッション番号NP_055148.3で登録されている下記のアミノ酸配列（配列番号１６）があげられる。配列番号１５の塩基配列は、配列番号１６のアミノ酸配列をコードする配列である。 Human-derived CADM1 can be used as a cDNA, for example, as a protein in the underlined region (130-1458th) of the following nucleotide sequence (SEQ ID NO: 15) registered at NCBI Accession No. NM_014333.3 (including stop codons). For example, the following amino acid sequence (SEQ ID NO: 16) registered under NCBI accession number NP_055148.3 can be mentioned. The nucleotide sequence of SEQ ID NO: 15 is a sequence encoding the amino acid sequence of SEQ ID NO: 16.
ヒト由来ＣＡＤＭ１　ｃＤＮＡ（配列番号１５）
5'-GGTTGGGCTCGCGGCGCTGTGATTGGTCTGCCCGGACTCCGCCTCCAGCGCATGTCATTAGCATCTCATTAGCTGTCCGCTCGGGCTCCGGAGGCAGCCAACGCCGCCAGTCTGAGGCAGGTGCCCGACATGGCGAGTGTAGTGCTGCCGAGCGGATCCCAGTGTGCGGCGGCAGCGGCGGCGGCGGCGCCTCCCGGGCTCCGGCTCCGGCTTCTGCTGTTGCTCTTCTCCGCCGCGGCACTGATCCCCACAGGTGATGGGCAGAATCTGTTTACGAAAGACGTGACAGTGATCGAGGGAGAGGTTGCGACCATCAGTTGCCAAGTCAATAAGAGTGACGACTCTGTGATTCAGCTACTGAATCCCAACAGGCAGACCATTTATTTCAGGGACTTCAGGCCTTTGAAGGACAGCAGGTTTCAGTTGCTGAATTTTTCTAGCAGTGAACTCAAAGTATCATTGACAAACGTCTCAATTTCTGATGAAGGAAGATACTTTTGCCAGCTCTATACCGATCCCCCACAGGAAAGTTACACCACCATCACAGTCCTGGTCCCACCACGTAATCTGATGATCGATATCCAGAAAGACACTGCGGTGGAAGGTGAGGAGATTGAAGTCAACTGCACTGCTATGGCCAGCAAGCCAGCCACGACTATCAGGTGGTTCAAAGGGAACACAGAGCTAAAAGGCAAATCGGAGGTGGAAGAGTGGTCAGACATGTACACTGTGACCAGTCAGCTGATGCTGAAGGTGCACAAGGAGGACGATGGGGTCCCAGTGATCTGCCAGGTGGAGCACCCTGCGGTCACTGGAAACCTGCAGACCCAGCGGTATCTAGAAGTACAGTATAAGCCTCAAGTGCACATTCAGATGACTTATCCTCTACAAGGCTTAACCCGGGAAGGGGACGCGCTTGAGTTAACATGTGAAGCCATCGGGAAGCCCCAGCCTGTGATGGTAACTTGGGTGAGAGTCGATGATGAAATGCCTCAACACGCCGTACTGTCTGGGCCCAACCTGTTCATCAATAACCTAAACAAAACAGATAATGGTACATACCGCTGTGAAGCTTCAAACATAGTGGGGAAAGCTCACTCGGATTATATGCTGTATGTATACGATCCCCCCACAACTATCCCTCCTCCCACAACAACCACCACCACCACCACCACCACCACCACCACCATCCTTACCATCATCACAGATTCCCGAGCAGGTGAAGAAGGCTCGATCAGGGCAGTGGATCATGCCGTGATCGGTGGCGTCGTGGCGGTGGTGGTGTTCGCCATGCTGTGCTTGCTCATCATTCTGGGGCGCTATTTTGCCAGACATAAAGGTACATACTTCACTCATGAAGCCAAAGGAGCCGATGACGCAGCAGACGCAGACACAGCTATAATCAATGCAGAAGGAGGACAGAACAACTCCGAAGAAAAGAAAGAGTACTTCATCTAGATCAGCCTTTTTGTTTCAATGAGGTGTCCAACTGGCCCTATTTAGATGATAAAGAGACAGTGATATTGGAACTTGCGAGAAATTCGTGTGTTTTTTTATGAATGGGTGGAAAGGTGTGAGACTGGGAAGGCTTGGGATTTGCTGTGTAAAAAAAAAAAAAATGTTCTTTGGAAAGTACACTCTGCTGTTTGACACCTCTTTTTTCGTTTGTTTGTTTGTTTAATTTTTATTTCTTCCTACCAAGTCAAACTTGGATACTTGGATTTAGTTTCAGTAGATTGCAGAAAATTCTGTGCCTTGTTTTTTGTTTGTTTGTTGCGTTCCTTTCTTTTCCCCCTTTGTGCACATTTATTTCCTCCCTCTACCCCAATTTCGGATTTTTTCCAAAATCTCCCATTTTGGAATTTGCCTGCTGGGATTCCTTAGACTCTTTTCCTTCCCTTTTCTGTTCTAGTTTTTTACTTTTGTTTATTTTTATGGTAACTGCTTTCTGTTCCAAATTCAGTTTCATAAAAGGAGAACCAGCACAGCTTAGATTTCATAGTTCAGAATTTAGTGTATCCATAATGCATTCTTCTCTGTTGTCGTAAAGATTTGGGTGAACAAACAATGAAAACTCTTTGCTGCTGCCCATGTTTCAAATACTTAGAGCAGTGAAGACTAGAAAATTAGACTGTGATTCAGAAAATGTTCTGTTTGCTGTGGAACTACATTACTGTACAGGGTTATCTGCAAGTGAGGTGTGTCACAATGAGATTGAATTTCACTGTCTTTAATTCTGTATCTGTAGACGGCTCAGTATAGATACCCTACGCTGTCCAGAAAGGTTTGGGGCAGAAAGGACTCCTCCTTTTTCCATGCCCTAAACAGACCTGACAGGTGAGGTCTGTTCCTTTTATATAAGTGGACAAATTTTGAGTTGCCACAGGAGGGGAAGTAGGGAGGGGGGAAATACAGTTCTGCTCTGGTTGTTTCTGTTCCAAATGATTCCATCCACCTTTCCCAATCGGCCTTACTTCTCACTAATTTGTAGGAAAAAGCAAGTTCGTCTGTTGTGCGAATGACTGAATGGGACAGAGTTGATTTTTTTTTTTTTTTCCTTTGTGCTTAGTTAGGAAGGCAGTAGGATGTGGCCTGCATGTACTGTATATTACAGATATTTGTCATGCTGGGATTTCCAACTCGAATCTGTGTGAAACTTTCATTCCTTCAGATTTGGCTTGACAAAGGCAGGAGGTACAAAAGAAGGGCTGGTATTGTTCTCACACTGGTCTGCTGTCGCTCTCAGTTCTCGATAGGTCAGAGCAGAGGTGGAAAAACAGCATGTACGGATTTTCAGTTACTTAATCAAAACTCAAATGTGAGTGTTTTTATCTTTTTACCTTTCATACACTAGCCTTGGCCTCTTTCCTCAGCCTTAAGAACCATCTGCCAAAAATTACTGATCCTCGCATGATGGCAGCCATAGTGCATAGCTACTAAAATCAGTGACCTTGAACATATCTTAGATGGGGAGCCTCGGGAAAAGGTAGAGGAGTCACGTTACCATTTACATGTTTTAAAGAAAGAAGTGTGGGGATTTTCACTGAAACGTCTAGGAAATCTAGAAGTAGTCCTGAAGGACAGAAACTAAACTCTTACCATATGTTTGGTAAGACTCCAGACTCCAGCTAACAGTCCCTATGGAAAGATGGCATCAAAAAAGATAGATCTATATATATATATAAATATATATTCTATTACATTTTCAGTGAGTAATTTTGGATTTTGCAAGGTGCATTTTTACTATTGTTACATTATGTGGAAAACTTATGCTGATTTATTTAAGGGGGAAAAAGTGTCAACTCTTTGTTATTTGAAAACATGTTTATTTTTCTTGTCTTTATTTTAACCTTTGATAGAACCATTGCAATATGGGGGCCTTTTGGGAACGGACTGGTATGTAAAAGAAAATCCATTATCGAGCAGCATTTTATTTACCCCTCCCCTATCCCTAGGCACTTAACCAAGACAAAAAGCCACAATGAACATCCCTTTTTCAATGAATTTTATAATCTGCAGCTCTATTCCGAGCCCTTAGCACCCATTCCGACCATAGTATAATCATATCAAAGGGTGAGAATCATTTAGCATGTTGTTGAAAGGTTTTTTTTCAGTTGTTCTTTTTAGAAAAAAAGAAAAACAAAAACAAAAACAAAAAAAAAAAATCACACCATTGCTCACAGAATTGGCATCTCATTTTTGGGACCTCCCATCTTTCTGTTTTGAAAAGTGTACAGTAGTGCAGTGTTCCTGATGTAACTTTATGGCTTACAATGTTGACATGTCTCAGGTTCATGTGTTGCGATTGGTGTTTTCCGTCTCAGGTAGATTGCAAAGTGTAGGCCCCACACATTGGAAAAAATAATAATAAAACAAAGCAAAAACAGGAAATTATGGATTTTAGTTGTATATTGGTTTATGTATTTTTTCTTAAGTATACAGTGCACTGTTTGAAATGTATTGTTGAGTATTACTTTGTACAGGTTGATCACTTTTTTTAGAGTGAAGAAAGAACAAACTTGTTTTTTGTGTTTTTTAAAGGAATATAAAATAATGAAGGATGTATAATTGATGCCAAATAAGCTTGTTCTTTAGTCACACCGACGTCTTATTTTTCCCTTTAGGCCAGTTCTGTTTTTAAGGTGTACATGGACAATGTTACAGTGTAAGAAACTCCATATCCATATGTTCCCATTCGCATTTTGTATTGGTTCATGTATACCATTTTTACAAAAAAAAAAAGAAAAAAAAGAAGTACTATAAAATATCTGTCTTCTTAATAAAAAAAAATTAATGTTACAAAGTGAAAAAAAAAAAAAAAAAA-3' Human-derived CADM1 cDNA (SEQ ID NO: 15)
5'-GGTTGGGCTCGCGGCGCTGTGATTGGTCTGCCCGGACTCCGCCTCCAGCGCATGTCATTAGCATCTCATTAGCTGTCCGCTCGGGCTCCGGAGGCAGCCAACGCCGCCAGTGTGAGGCAGGTGCCCGAC ATGGCGAGTGTAGTGCTGCCGAGCGGATCCCAGTGTGCGGCGGCAGCGGCGGCGGCGGCGCCTCCCGGGCTCCGGCTCCGGCTTCTGCTGTTGCTCTTCTCCGCCGCGGCACTGATCCCCACAGGTGATGGGCAGAATCTGTTTACGAAAGACGTGACAGTGATCGAGGGAGAGGTTGCGACCATCAGTTGCCAAGTCAATAAGAGTGACGACTCTGTGATTCAGCTACTGAATCCCAACAGGCAGACCATTTATTTCAGGGACTTCAGGCCTTTGAAGGACAGCAGGTTTCAGTTGCTGAATTTTTCTAGCAGTGAACTCAAAGTATCATTGACAAACGTCTCAATTTCTGATGAAGGAAGATACTTTTGCCAGCTCTATACCGATCCCCCACAGGAAAGTTACACCACCATCACAGTCCTGGTCCCACCACGTAATCTGATGATCGATATCCAGAAAGACACTGCGGTGGAAGGTGAGGAGATTGAAGTCAACTGCACTGCTATGGCCAGCAAGCCAGCCACGACTATCAGGTGGTTCAAAGGGAACACAGAGCTAAAAGGCAAATCGGAGGTGGAAGAGTGGTCAGACATGTACACTGTGACCAGTCAGCTGATGCTGAAGGTGCACAAGGAGGACGATGGGGTCCCAGTGATCTGCCAGGTGGAGCACCCTGCGGTCACTGGAAACCTGCAGACCCAGCGGTATCTAGAAGTACAGTATAAGCCTCAAGTGCACATTCAGATGACTTATCCTCTACAAGGCTTAACCCGGGAAGGGGACGCGCTTGAGTTAACATGTGAAGCCATCGGGAAGCCCCAGCCTGTGATGGTAACTTGGGTGAGAGTCGATGATGAAATGCCTCAACACGCCGTACTGTCTGGGCCCAACCTGTTCATCAATAACCTAAACAAAACAGATAATGGTACATACCGCTGTGAAGCTTCAAACATAGTGGGGAAAGCTCACTCGGATTATATGCTGTATGTATACGATCCCCCCACAACTATCCCTCCTCCCACAACAACCACCACCACCACCACCACCACCACCACCACCATCCTTACCATCATCACAGATTCCCGAGCAGGTGAAGAAGGCTCGATCAGGGCAGTGGATCATGCCGTGATCGGTGGCGTCGTGGCGGTGGTGGTGTTCGCCATGCTGTGCTTGCTCATCATTCTGGGGCGCTATTTTGCCAGACATAAAGGTACATACTTCACTCATGAAGCCAAAGGAGCCGATGACGCAGCAGACGCAGACACAGCTATAATCAATGCAGAAGGAGGACAGAACAACTCCGAAGAAAAGAAAGAGTACTTCATCTAG -3'
ヒト由来ＣＡＤＭ１　タンパク質（配列番号１６）
MASVVLPSGSQCAAAAAAAAPPGLRLRLLLLLFSAAALIPTGDGQNLFTKDVTVIEGEVATISCQVNKSDDSVIQLLNPNRQTIYFRDFRPLKDSRFQLLNFSSSELKVSLTNVSISDEGRYFCQLYTDPPQESYTTITVLVPPRNLMIDIQKDTAVEGEEIEVNCTAMASKPATTIRWFKGNTELKGKSEVEEWSDMYTVTSQLMLKVHKEDDGVPVICQVEHPAVTGNLQTQRYLEVQYKPQVHIQMTYPLQGLTREGDALELTCEAIGKPQPVMVTWVRVDDEMPQHAVLSGPNLFINNLNKTDNGTYRCEASNIVGKAHSDYMLYVYDPPTTIPPPTTTTTTTTTTTTTILTIITDSRAGEEGSIRAVDHAVIGGVVAVVVFAMLCLLIILGRYFARHKGTYFTHEAKGADDAADADTAIINAEGGQNNSEEKKEYFI Human-derived CADM1 protein (SEQ ID NO: 16)
MASVVLPSGSQCAAAAAAAAPPGLRLRLLLLLFSAAALIPTGDGQNLFTKDVTVIEGEVATISCQVNKSDDSVIQLLNPNRQTIYFRDFRPLKDSRFQLLNFSSSELKVSLTNVSISDEGRYFCQLYTDPPQESYTTITVLVPPRNLMIDIQKDTAVEGEEIEVNCTAMASKPATTIRWFKGNTELKGKSEVEEWSDMYTVTSQLMLKVHKEDDGVPVICQVEHPAVTGNLQTQRYLEVQYKPQVHIQMTYPLQGLTREGDALELTCEAIGKPQPVMVTWVRVDDEMPQHAVLSGPNLFINNLNKTDNGTYRCEASNIVGKAHSDYMLYVYDPPTTIPPPTTTTTTTTTTTTTILTIITDSRAGEEGSIRAVDHAVIGGVVAVVVFAMLCLLIILGRYFARHKGTYFTHEAKGADDAADADTAIINAEGGQNNSEEKKEYFI
　ヒト由来ＲＮＦ１２８は、ｃＤＮＡとして、例えば、ＮＣＢＩアクセッション番号NM_194463.2で登録されている下記の塩基配列（配列番号１７）における下線部（214－1500）番目の領域（終始コドン含む）、タンパク質として、例えば、ＮＣＢＩアクセッション番号NP_919445.1で登録されている下記のアミノ酸配列（配列番号１８）があげられる。配列番号１７の塩基配列は、配列番号１８のアミノ酸配列をコードする配列である。 Human-derived RNF128 can be used as a cDNA, for example, as a protein in the underlined region (214-1500) (including stop codons) in the following nucleotide sequence (SEQ ID NO: 17) registered at NCBI Accession No. NM_194463.2. For example, the following amino acid sequence (SEQ ID NO: 18) registered under NCBI accession number NP_919445.1 can be mentioned. The nucleotide sequence of SEQ ID NO: 17 is a sequence encoding the amino acid sequence of SEQ ID NO: 18.
ヒト由来ＲＮＦ１２８　ｃＤＮＡ（配列番号１７）
5'-GCGGTAGCGGAGAAGACTGGAGCTCCGAGGAGCTGCATCTGCGGCAACCTGTGTGCTGACGCTACGTGCCTCCTGGCTCCGACGTAGCTCGCAGCTCCCCAGTCTCACTCCATTCCTTCCCCACCTGGCGCGCACCTGCTCAAGACCAGGGTCCTGCCAAGCGCTAGGAGGGCGCGTGCCAGGGGCGCTAGGGAACTGCGGAGCGCGCGCGCCATGGGGCCGCCGCCTGGGGCCGGGGTCTCCTGCCGCGGTGGCTGCGGCTTTTCCAGATTGCTGGCATGGTGCTTCCTGCTGGCCCTGAGTCCGCAGGCACCCGGTTCCCGGGGGGCTGAAGCAGTGTGGACCGCGTACCTCAACGTGTCCTGGCGGGTTCCGCACACGGGAGTGAACCGTACGGTGTGGGAGCTGAGCGAGGAGGGCGTGTACGGCCAGGACTCGCCGCTGGAGCCTGTGGCTGGGGTCCTGGTACCGCCCGACGGGCCCGGGGCGCTTAACGCCTGTAACCCGCACACGAATTTCACGGTGCCCACGGTTTGGGGAAGCACCGTGCAAGTCTCTTGGTTGGCCCTCATCCAACGCGGCGGGGGCTGCACCTTCGCAGACAAGATCCATCTGGCTTATGAGAGAGGGGCGTCTGGAGCCGTCATCTTTAACTTCCCCGGGACCCGCAATGAGGTCATCCCCATGTCTCACCCGGGTGCAGTAGACATTGTTGCAATCATGATCGGCAATCTGAAAGGCACAAAAATTCTGCAATCTATTCAAAGAGGCATACAAGTGACAATGGTCATAGAAGTAGGGAAAAAACATGGCCCTTGGGTGAATCACTATTCAATTTTTTTCGTTTCTGTGTCCTTTTTTATTATTACGGCGGCAACTGTGGGCTATTTTATCTTTTATTCTGCTCGAAGGCTACGGAATGCAAGAGCTCAAAGCAGGAAGCAGAGGCAATTAAAGGCAGATGCTAAAAAAGCTATTGGAAGGCTTCAACTACGCACACTGAAACAAGGAGACAAGGAAATTGGCCCTGATGGAGATAGTTGTGCTGTGTGCATTGAATTGTATAAACCAAATGATTTGGTACGCATCTTAACGTGCAACCATATTTTCCATAAGACATGTGTTGACCCATGGCTGTTAGAACACAGGACTTGCCCCATGTGCAAATGTGACATACTCAAAGCTTTGGGAATTGAGGTGGATGTTGAAGATGGATCAGTGTCTTTACAAGTCCCTGTATCCAATGAAATATCTAATAGTGCCTCCTCCCATGAAGAGGATAATCGCAGCGAGACCGCATCATCTGGATATGCTTCAGTACAGGGAACAGATGAACCGCCTCTGGAGGAACACGTGCAGTCAACAAATGAAAGTCTACAGCTGGTAAACCATGAAGCAAATTCTGTGGCAGTGGATGTTATTCCTCATGTTGACAACCCAACCTTTGAAGAAGACGAAACTCCTAATCAAGAGACTGCTGTTCGAGAAATTAAATCTTAAAATCTGTGTAAATAGAAAACTTGAACCATTAGTAATAACAGAACTGCCAATCAGGGCCTAGTTTCTATTAATAAATTGGATAAATTTAATAAAATAAGAGTGATACTGAAAGTGCTCAGATGACTAATATTATGCTATAGTTAAATGGCTTAAAATATTTAACCTGTTAACTTTTTTCCACAAACTCATTATAATATTTTTCATAGGCAAGTTTCCTCTCAGTAGTGATAACAACATTTTTAGACATTCAAAACTGTCTTCAAGAAGTCACGTTTTTCATTTATAACAATTTTCTTATAAAAACATGTTGCTTTTAAAATGTGGAGTAGCTGTAATCACTTTATTTTATGATAGTATCTTAATGAAAAATACTACTTCTTTAGCTTGGGCTACATGTGTCAGGGTTTTTCTCCAGGTGCTTATATTGATCTGGAATTGTAATGTAAAAAGCAATGCAAACTTAGGCGAGTACTTCTTGAAATGTCTATTTAAGCTGCTTTAAGTTAATAGAAAAGATTAAAGCAAAATATTCATTTTTACTTTTTCTTATTTTTAAAATTAGGCTGAATGTACTTCATGTGATTTGTCAACCATAGTTTATCAGAGATTATGGACTTAATTGATTGGTATATTAGTGACATCAACTTGACACAAGATTAGACAAAAAATTCCTTACAAAAATACTGTGTAACTATTTCTCAAACTTGTGGGATTTTTCAAAAGCTCAGTATATGAATCATCATACTGTTTGAAATTGCTAATGACAGAGTAAGTAACACTAATATTGGTCATTGATCTTCGTTCATGAATTAGTCTACAGAAAAAAAATGTTCTGTAAAATTAGTCTGTTGAAAATGTTTTCCAAACAATGTTACTTTGAAAATTGAGTTTATGTTTGACCTAAATGGGCTAAAATTACATTAGATAAACTAAAATTCTGTCCGTGTAACTATAAATTTTGTGAATGCATTTTCCTGGTGTTTGAAAAAGAAGGGGGGGAGAATTCCAGGTGCCTTAATATAAAGTTTGAAGCTTCATCCACCAAAGTTAAATAGAGCTATTTAAAAATGCACTTTATTTGTACTCTGTGTGGCTTTTGTTTTAGAATTTTGTTCAAATTATAGCAGAATTTAGGCAAAAATAAAACAGACATGTATTTTTGTTTGCTGAATGGATGAAACCATTGCATTCTTGTACACTGATTTGAAATGCTGTAAATATGTCCCAATTTGTATTGATTCTCTTTAAATATAAAATGTAAATAAAATATTCCAATAAAAGTTTGTGTCTGGTGTTAGTTTAA-3' Human-derived RNF128 cDNA (SEQ ID NO: 17)
5'-GCGGTAGCGGAGAAGACTGGAGCTCCGAGGAGCTGCATCTGCGGCAACCTGTGTGCTGACGCTACGTGCCTCCGTCCGCGCGTAGCCTCGCAGCTCCCCAGTCACTCCATTCCTTCCCCACCTGGCGCGCACCTGCGCGCGCGCGCGCGCG ATGGGGCCGCCGCCTGGGGCCGGGGTCTCCTGCCGCGGTGGCTGCGGCTTTTCCAGATTGCTGGCATGGTGCTTCCTGCTGGCCCTGAGTCCGCAGGCACCCGGTTCCCGGGGGGCTGAAGCAGTGTGGACCGCGTACCTCAACGTGTCCTGGCGGGTTCCGCACACGGGAGTGAACCGTACGGTGTGGGAGCTGAGCGAGGAGGGCGTGTACGGCCAGGACTCGCCGCTGGAGCCTGTGGCTGGGGTCCTGGTACCGCCCGACGGGCCCGGGGCGCTTAACGCCTGTAACCCGCACACGAATTTCACGGTGCCCACGGTTTGGGGAAGCACCGTGCAAGTCTCTTGGTTGGCCCTCATCCAACGCGGCGGGGGCTGCACCTTCGCAGACAAGATCCATCTGGCTTATGAGAGAGGGGCGTCTGGAGCCGTCATCTTTAACTTCCCCGGGACCCGCAATGAGGTCATCCCCATGTCTCACCCGGGTGCAGTAGACATTGTTGCAATCATGATCGGCAATCTGAAAGGCACAAAAATTCTGCAATCTATTCAAAGAGGCATACAAGTGACAATGGTCATAGAAGTAGGGAAAAAACATGGCCCTTGGGTGAATCACTATTCAATTTTTTTCGTTTCTGTGTCCTTTTTTATTATTACGGCGGCAACTGTGGGCTATTTTATCTTTTATTCTGCTCGAAGGCTACGGAATGCAAGAGCTCAAAGCAGGAAGCAGAGGCAATTAAAGGCAGATGCTAAAAAAGCTATTGGAAGGCTTCAACTACGCACACTGAAACAAGGAGACAAGGAAATTGGCCCTGATGGAGATAGTTGTGCTGTGTGCATTGAATTGTATAAACCAAATGATTTGGTACGCATCTTAACGTGCAACCATATTTTCCATAAGACATGTGTTGACCCATGGCTGTTAGAACACAGGACTTGCCCCATGTGCAAATGTGACATACTCAAAGCTTTGGGAATTGAGGTGGATGTTGAAGATGGATCAGTGTCTTTACAAGTCCCTGTATCCAATGAAATATCTAATAGTGCCTCCTCCCATGAAGAGGATAATCGCAGCGAGACCGCATCATCTGGATATGCTTCAGTACAGGGAACAGATGAACCGCCTCTGGAGGAACACGTGCAGTCAACAAATGAAAGTCTACAGCTGGTAAACCATGAAGCAAATTCTGTGGCAGTGGATGTTATTCCTCATGTTGACAACCCAACCTTTGAAGAAGACGAAACTCCTAATCAAGAGACTGCTGTTCGAGAAATTAAATCTTAA -3'
ヒト由来ＲＮＦ１２８　タンパク質（配列番号１８）
MGPPPGAGVSCRGGCGFSRLLAWCFLLALSPQAPGSRGAEAVWTAYLNVSWRVPHTGVNRTVWELSEEGVYGQDSPLEPVAGVLVPPDGPGALNACNPHTNFTVPTVWGSTVQVSWLALIQRGGGCTFADKIHLAYERGASGAVIFNFPGTRNEVIPMSHPGAVDIVAIMIGNLKGTKILQSIQRGIQVTMVIEVGKKHGPWVNHYSIFFVSVSFFIITAATVGYFIFYSARRLRNARAQSRKQRQLKADAKKAIGRLQLRTLKQGDKEIGPDGDSCAVCIELYKPNDLVRILTCNHIFHKTCVDPWLLEHRTCPMCKCDILKALGIEVDVEDGSVSLQVPVSNEISNSASSHEEDNRSETASSGYASVQGTDEPPLEEHVQSTNESLQLVNHEANSVAVDVIPHVDNPTFEEDETPNQETAVREIKS Human-derived RNF128 protein (SEQ ID NO: 18)
MGPPPGAGVSCRGGCGFSRLLAWCFLLALSPQAPGSRGAEAVWTAYLNVSWRVPHTGVNRTVWELSEEGVYGQDSPLEPVAGVLVPPDGPGALNACNPHTNFTVPTVWGSTVQVSWLALIQRGGGCTFADKIHLAYERGASGAVIFNFPGTRNEVIPMSHPGAVDIVAIMIGNLKGTKILQSIQRGIQVTMVIEVGKKHGPWVNHYSIFFVSVSFFIITAATVGYFIFYSARRLRNARAQSRKQRQLKADAKKAIGRLQLRTLKQGDKEIGPDGDSCAVCIELYKPNDLVRILTCNHIFHKTCVDPWLLEHRTCPMCKCDILKALGIEVDVEDGSVSLQVPVSNEISNSASSHEEDNRSETASSGYASVQGTDEPPLEEHVQSTNESLQLVNHEANSVAVDVIPHVDNPTFEEDETPNQETAVREIKS
　ヒト由来ＡＴＰ６Ｖ１Ｂ１は、ｃＤＮＡとして、例えば、ＮＣＢＩアクセッション番号NM_001692.4で登録されている下記の塩基配列（配列番号１９）における下線部（56－1597）番目の領域（終始コドン含む）、タンパク質として、例えば、ＮＣＢＩアクセッション番号NP_001683.2で登録されている下記のアミノ酸配列（配列番号２０）があげられる。配列番号１９の塩基配列は、配列番号２０のアミノ酸配列をコードする配列である。 Human-derived ATP6V1B1 is used as a cDNA, for example, as a protein in the underlined region (56-1597) (including stop codons) in the following nucleotide sequence (SEQ ID NO: 19) registered at NCBI Accession No. NM_001692.4. For example, the following amino acid sequence (SEQ ID NO: 20) registered under NCBI accession number NP_001683.2. The nucleotide sequence of SEQ ID NO: 19 is a sequence encoding the amino acid sequence of SEQ ID NO: 20.
ヒト由来ＡＴＰ６Ｖ１Ｂ１　ｃＤＮＡ（配列番号１９）
5'-AGAGCTGCCACCAGCAGCAGGCTCAGACACTGGGCTCCCAGCTGGGGACTGCTCCATGGCCATGGAGATAGACAGCAGGCCTGGGGGGCTCCCCGGCAGTAGCTGCAACCTAGGTGCAGCCCGAGAACACATGCAGGCGGTCACCCGAAACTACATCACCCACCCCCGTGTCACCTACAGGACTGTGTGCAGCGTGAACGGGCCCCTGGTGGTGCTGGACCGGGTCAAGTTTGCCCAGTATGCGGAGATCGTCCACTTCACCCTCCCAGATGGGACTCAGAGGAGCGGGCAGGTGCTTGAGGTGGCTGGCACCAAGGCGATTGTTCAGGTGTTTGAAGGGACATCAGGGATCGATGCCAGGAAGACCACTTGCGAATTTACAGGGGACATCCTACGAACTCCGGTGTCAGAGGACATGCTGGGTCGGGTTTTCAATGGCTCCGGCAAGCCCATTGACAAGGGGCCAGTGGTCATGGCGGAGGACTTTCTGGATATCAATGGCCAGCCCATCAACCCGCACTCCCGCATCTACCCCGAGGAGATGATTCAGACGGGCATTTCTCCTATTGACGTCATGAACAGCATTGCCCGCGGCCAGAAGATCCCCATCTTCTCAGCAGCCGGGCTCCCCCACAATGAGATTGCCGCTCAGATCTGCCGCCAGGCGGGGCTGGTGAAGAAGTCCAAGGCTGTGCTGGATTACCATGACGACAACTTCGCCATCGTCTTTGCAGCCATGGGGGTGAACATGGAGACAGCCAGATTCTTCAAGTCTGACTTTGAGCAGAATGGAACCATGGGGAACGTCTGCCTCTTCCTGAACTTGGCCAATGACCCCACGATCGAGCGGATCATCACCCCGCGCCTGGCGCTGACCACTGCTGAATTCCTTGCCTACCAGTGTGAGAAGCATGTGCTGGTCATACTGACGGACATGAGTTCCTATGCAGAGGCCTTGCGGGAGGTCTCTGCTGCTAGAGAGGAGGTGCCTGGGCGCCGAGGGTTTCCTGGATATATGTACACAGACCTGGCCACCATCTACGAGCGGGCGGGCCGCGTGGAGGGTCGGGGAGGATCCATCACACAGATCCCCATCCTCACCATGCCCAACGACGATATCACCCACCCTATCCCAGACTTGACGGGCTTCATCACAGAGGGACAGATCTACGTGGACAGACAGCTTCACAACAGACAGATCTACCCCCCCATCAACGTGCTCCCTTCCCTGTCGCGGCTGATGAAGTCAGCCATTGGGGAAGGCATGACAAGAAAGGACCATGGAGATGTCTCCAACCAGCTGTACGCCTGCTATGCCATCGGGAAGGACGTGCAGGCCATGAAGGCAGTAGTTGGGGAGGAGGCGCTCACCTCTGAGGACCTGCTCTACCTGGAATTCCTGCAGAAGTTTGAGAAGAACTTCATCAATCAGGGCCCCTACGAGAACCGCTCGGTGTTCGAGTCGCTGGACCTGGGCTGGAAGCTGCTGCGCATCTTCCCCAAGGAGATGCTGAAGCGCATTCCGCAGGCCGTGATCGACGAGTTCTATTCCCGCGAGGGGGCGCTGCAGGACCTCGCGCCTGACACTGCGCTCTAGCCCCGCGCGCCGTGGCACCCCAACACCGGCAGGGAACCTACCCTCGGCTCCCGGGTCTCCCCTCCCTCGCCACCCCAACCAGCGGCTTCTGCGCCGCCCTCCGCCCTCCGCTGGCTCCGAGGTGGTGGGGGCGCCGCACGCTCCATCCCTTTCCCTCGCTCGATTCCTTTTCCCGCGCTCCATGCCTCCCCCTCGACTCCCGGTGCTGCGGAAGAACTGAAGGTTGCGATGCCTTACTCTGACGGGAGCATCTGTATTTTTATGTTAAAAGCCCACAAAATAAAAATAAAAAGTAACTGAGATGAATTTA-3' Human-derived ATP6V1B1 cDNA (SEQ ID NO: 19)
5'-AGAGCTGCCACCAGCAGCAGGCTCAGACACTGGGCTCCCAGCTGGGGACTGCTCC ATGGCCATGGAGATAGACAGCAGGCCTGGGGGGCTCCCCGGCAGTAGCTGCAACCTAGGTGCAGCCCGAGAACACATGCAGGCGGTCACCCGAAACTACATCACCCACCCCCGTGTCACCTACAGGACTGTGTGCAGCGTGAACGGGCCCCTGGTGGTGCTGGACCGGGTCAAGTTTGCCCAGTATGCGGAGATCGTCCACTTCACCCTCCCAGATGGGACTCAGAGGAGCGGGCAGGTGCTTGAGGTGGCTGGCACCAAGGCGATTGTTCAGGTGTTTGAAGGGACATCAGGGATCGATGCCAGGAAGACCACTTGCGAATTTACAGGGGACATCCTACGAACTCCGGTGTCAGAGGACATGCTGGGTCGGGTTTTCAATGGCTCCGGCAAGCCCATTGACAAGGGGCCAGTGGTCATGGCGGAGGACTTTCTGGATATCAATGGCCAGCCCATCAACCCGCACTCCCGCATCTACCCCGAGGAGATGATTCAGACGGGCATTTCTCCTATTGACGTCATGAACAGCATTGCCCGCGGCCAGAAGATCCCCATCTTCTCAGCAGCCGGGCTCCCCCACAATGAGATTGCCGCTCAGATCTGCCGCCAGGCGGGGCTGGTGAAGAAGTCCAAGGCTGTGCTGGATTACCATGACGACAACTTCGCCATCGTCTTTGCAGCCATGGGGGTGAACATGGAGACAGCCAGATTCTTCAAGTCTGACTTTGAGCAGAATGGAACCATGGGGAACGTCTGCCTCTTCCTGAACTTGGCCAATGACCCCACGATCGAGCGGATCATCACCCCGCGCCTGGCGCTGACCACTGCTGAATTCCTTGCCTACCAGTGTGAGAAGCATGTGCTGGTCATACTGACGGACATGAGTTCCTATGCAGAGGCCTTGCGGGAGGTCTCTGCTGCTAGAGAGGAGGTGCCTGGGCGCCGAGGGTTTCCTGGATATATGTACACAGACCTGGCCACCATCTACGAGCGGGCGGGCCGCGTGGAGGGTCGGGGAGGATCCATCACACAGATCCCCATCCTCACCATGCCCAACGACGATATCACCCACCCTATCCCAGACTTGACGGGCTTCATCACAGAGGGACAGATCTACGTGGACAGACAGCTTCACAACAGACAGATCTACCCCCCCATCAACGTGCTCCCTTCCCTGTCGCGGCTGATGAAGTCAGCCATTGGGGAAGGCATGACAAGAAAGGACCATGGAGATGTCTCCAACCAGCTGTACGCCTGCTATGCCATCGGGAAGGACGTGCAGGCCATGAAGGCAGTAGTTGGGGAGGAGGCGCTCACCTCTGAGGACCTGCTCTACCTGGAATTCCTGCAGAAGTTTGAGAAGAACTTCATCAATCAGGGCCCCTACGAGAACCGCTCGGTGTTCGAGTCGCTGGACCTGGGCTGGAAGCTGCTGCGCATCTTCCCCAAGGAGATGCTGAAGCGCATTCCGCAGGCCGTGATCGACGAGTTCTATTCCCGCGAGGGGGCGCTGCAGGACCTCGCGCCTGACACTGCGCTCTAG CCCCGCGCGCCGTGGCACCCCAACACCGGCAGGGAACCTACCCTCGGCTCCCGGGTCTCCCCTCCCTCGCCACCCCAACCAGCGGCTTCTGCGCCGCCCTCCGCCCTCCGCTGGCTCCGAGGTGGTGGGGGCGCCGCACGCTCCATCCCTTTCCCTCGCTCGATTCCTTTTCCCGCGCTCCATGCCTCCCCCTCGACTCCCGGTGCTGCGGAAGAACTGAAGGTTGCGATGCCTTACTCTGACGGGAGCATCTGTATTTTTATGTTAAAAGCCCACAAAATAAAAATAAAAAGTAACTGAGATGAATTTA-3 '
ヒト由来ＡＴＰ６Ｖ１Ｂ１　タンパク質（配列番号２０）
MAMEIDSRPGGLPGSSCNLGAAREHMQAVTRNYITHPRVTYRTVCSVNGPLVVLDRVKFAQYAEIVHFTLPDGTQRSGQVLEVAGTKAIVQVFEGTSGIDARKTTCEFTGDILRTPVSEDMLGRVFNGSGKPIDKGPVVMAEDFLDINGQPINPHSRIYPEEMIQTGISPIDVMNSIARGQKIPIFSAAGLPHNEIAAQICRQAGLVKKSKAVLDYHDDNFAIVFAAMGVNMETARFFKSDFEQNGTMGNVCLFLNLANDPTIERIITPRLALTTAEFLAYQCEKHVLVILTDMSSYAEALREVSAAREEVPGRRGFPGYMYTDLATIYERAGRVEGRGGSITQIPILTMPNDDITHPIPDLTGFITEGQIYVDRQLHNRQIYPPINVLPSLSRLMKSAIGEGMTRKDHGDVSNQLYACYAIGKDVQAMKAVVGEEALTSEDLLYLEFLQKFEKNFINQGPYENRSVFESLDLGWKLLRIFPKEMLKRIPQAVIDEFYSREGALQDLAPDTAL Human-derived ATP6V1B1 protein (SEQ ID NO: 20)
MAMEIDSRPGGLPGSSCNLGAAREHMQAVTRNYITHPRVTYRTVCSVNGPLVVLDRVKFAQYAEIVHFTLPDGTQRSGQVLEVAGTKAIVQVFEGTSGIDARKTTCEFTGDILRTPVSEDMLGRVFNGSGKPIDKGPVVMAEDFLDINGQPINPHSRIYPEEMIQTGISPIDVMNSIARGQKIPIFSAAGLPHNEIAAQICRQAGLVKKSKAVLDYHDDNFAIVFAAMGVNMETARFFKSDFEQNGTMGNVCLFLNLANDPTIERIITPRLALTTAEFLAYQCEKHVLVILTDMSSYAEALREVSAAREEVPGRRGFPGYMYTDLATIYERAGRVEGRGGSITQIPILTMPNDDITHPIPDLTGFITEGQIYVDRQLHNRQIYPPINVLPSLSRLMKSAIGEGMTRKDHGDVSNQLYACYAIGKDVQAMKAVVGEEALTSEDLLYLEFLQKFEKNFINQGPYENRSVFESLDLGWKLLRIFPKEMLKRIPQAVIDEFYSREGALQDLAPDTAL
　本発明のがんマーカーは、例えば、よりマーカーとしての精度が高いことから、抗ヒト由来ＨＩＲＩＰ３抗体、抗ヒト由来ＦＮＤＣ１１抗体、抗ヒト由来ＳＬＣ１Ａ３抗体、および抗ヒト由来ＴＭＥＭ３３抗体からなる群から選択される少なくとも１つの抗体を含むことが好ましく、抗ヒト由来ＨＩＲＩＰ３抗体を含むことがより好ましい。 The cancer marker of the present invention is selected from the group consisting of anti-human-derived HIRIP3 antibody, anti-human-derived FNDC11 antibody, anti-human-derived SLC1A3 antibody, and anti-human-derived TMEM33 antibody, for example, because of its higher accuracy as a marker. It is preferable to contain at least one antibody, and more preferably to contain an anti-human-derived HIRIP3 antibody.
　本発明のがんマーカーは、１種類を用いてもよいし、２種類以上を併用してもよい。後者の場合、本発明のがんマーカーの組合せは、特に制限されず、任意のがんマーカーの組合せとできる。具体例として、本発明のがんマーカーの組合せは、よりマーカーとしての精度が高いことから、抗ヒト由来ＨＩＲＩＰ３抗体、抗ヒト由来ＦＮＤＣ１１抗体、抗ヒト由来ＳＬＣ１Ａ３抗体、および抗ヒト由来ＴＭＥＭ３３抗体を含むことが好ましい。 The cancer marker of the present invention may be used alone or in combination of two or more. In the latter case, the combination of cancer markers of the present invention is not particularly limited and can be any combination of cancer markers. As a specific example, the combination of cancer markers of the present invention includes an anti-human-derived HIRIP3 antibody, an anti-human-derived FNDC11 antibody, an anti-human-derived SLC1A3 antibody, and an anti-human-derived TMEM33 antibody because of its higher accuracy as a marker. Is preferable.
　前記本発明の抗体および抗原タンパク質は、がんマーカーとして使用でき、具体的には、例えば、乳がん、卵巣がん、膵がん、肝臓がん、胆管がん、大腸がん、結腸がん、直腸がん、胃がん、口腔がん、肺がんのがんマーカーとして使用でき、より精度よく検出できることから乳がんマーカーとして使用することが好ましい。前記がんは、乳がんが好ましい。前記乳がんは、特に制限されず、例えば、乳管がん、小葉がん等があげられる。本発明のがんマーカーによれば、例えば、原発巣のがんおよび転移がんのいずれであっても試験できる。 The antibody and antigen protein of the present invention can be used as cancer markers, and specifically, for example, breast cancer, ovarian cancer, pancreatic cancer, liver cancer, bile duct cancer, colon cancer, colon cancer, and the like. It can be used as a cancer marker for rectal cancer, gastric cancer, oral cancer, and lung cancer, and is preferably used as a breast cancer marker because it can be detected more accurately. Breast cancer is preferable as the cancer. The breast cancer is not particularly limited, and examples thereof include ductal carcinoma and lobular cancer. According to the cancer marker of the present invention, for example, either a primary tumor or a metastatic cancer can be tested.
　本発明のマーカーは、例えば、前記本発明の抗体および抗原タンパク質でもよいし、前記本発明の抗体および抗原タンパク質の遺伝子から転写されたｍＲＮＡでもよい。 The marker of the present invention may be, for example, the antibody and antigen protein of the present invention, or mRNA transcribed from the gene of the antibody and antigen protein of the present invention.
（がんの罹患危険度の試験方法）
　本発明のがんの罹患危険度の試験方法は、前述のように、被検者の生体試料におけるがんマーカーの発現量を測定する工程（測定工程）を含み、前記がんマーカーが、前記本発明のがんマーカーを含むことを特徴とする。本発明は、がんマーカーとして、前記本発明の抗体および抗原タンパク質の発現量を測定することが特徴であって、その他の工程および条件は、特に制限がない。本発明の試験方法は、前記本発明のがんマーカーの説明を援用できる。 (Test method for cancer risk)
As described above, the method for testing the risk of developing cancer of the present invention includes a step (measurement step) of measuring the expression level of a cancer marker in a biological sample of a subject, and the cancer marker is the above-mentioned. It is characterized by containing the cancer marker of the present invention. The present invention is characterized in that the expression level of the antibody and antigen protein of the present invention is measured as a cancer marker, and other steps and conditions are not particularly limited. The test method of the present invention can be referred to the description of the cancer marker of the present invention.
　本発明の試験方法によれば、例えば、がんの発症の可能性、がんの発症の有無（がん化しているか否か）、がんの進行度および予後の状態等を評価できる。対象となるがんは、前述のように、例えば、乳がん、卵巣がん、膵がん、肝臓がん、胆管がん、大腸がん、結腸がん、直腸がん、胃がん、口腔がん、肺がん等があげられ、より精度よく検出できることから、乳がんが好ましい。また、本発明の試験方法によれば、例えば、原発巣のがん、転移がんのいずれであっても試験できる。 According to the test method of the present invention, for example, the possibility of developing cancer, the presence or absence of the onset of cancer (whether or not it has become cancerous), the degree of cancer progression, the state of prognosis, and the like can be evaluated. As mentioned above, the target cancers are, for example, breast cancer, ovarian cancer, pancreatic cancer, liver cancer, bile duct cancer, colon cancer, colon cancer, rectal cancer, stomach cancer, oral cancer, etc. Breast cancer is preferable because lung cancer and the like can be detected more accurately. Further, according to the test method of the present invention, for example, either a primary tumor or a metastatic cancer can be tested.
　本発明の試験方法において、前記被検者は、例えば、ヒト、ヒトを除く非ヒト動物等があげられ、前記非ヒト動物は、前述のように、例えば、マウス、ラット、イヌ、サル、ウサギ、ヒツジ、ウマ等の哺乳類があげられる。 In the test method of the present invention, the subject includes, for example, humans, non-human animals other than humans, and the non-human animals include, for example, mice, rats, dogs, monkeys, and rabbits, as described above. , Sheep, horses and other mammals.
　本発明の試験方法において、前記生体試料の種類は、特に制限されず、例えば、生体から分離した、体液、体液由来細胞、器官、組織または細胞等があげられる。前記体液は、例えば、血液試料があげられ、具体例として、例えば、全血、血清、血漿等があげられる。前記体液由来細胞は、例えば、血液由来細胞があげられ、具体的には、血球、白血球、リンパ球等の血球細胞があげられる。前記生体試料は、例えば、試験対象のがんの種類に応じて、適宜決定できる。前記生体試料は、例えば、試験対象のがんが発生しうる器官由来である。前記器官は、例えば、乳房、卵巣、膵臓、肝臓、胆管、大腸、結腸、直腸、胃、口腔細胞、肺等である。具体例として、前記がんが乳がんの場合、例えば、乳腺、乳管等の乳房由来の組織または細胞が好ましい。また、本発明の試験方法によれば、例えば、がんを血液中の前記本発明のがんマーカーの発現量によって試験できる。このため、例えば、患者や医師の負担を軽減できることから、前記生体試料は、全血、血清、または血漿が好ましく、より好ましくは、血清または血漿である。 In the test method of the present invention, the type of the biological sample is not particularly limited, and examples thereof include body fluids, body fluid-derived cells, organelles, tissues, and cells separated from the living body. Examples of the body fluid include blood samples, and specific examples thereof include whole blood, serum, and plasma. Examples of the body fluid-derived cells include blood-derived cells, and specific examples thereof include blood cell cells such as blood cells, white blood cells, and lymphocytes. The biological sample can be appropriately determined, for example, according to the type of cancer to be tested. The biological sample is, for example, derived from an organ in which the cancer under test can develop. The organs are, for example, breast, ovary, pancreas, liver, bile duct, large intestine, colon, rectum, stomach, oral cells, lung and the like. As a specific example, when the cancer is breast cancer, for example, breast-derived tissues or cells such as mammary glands and ducts are preferable. Further, according to the test method of the present invention, for example, cancer can be tested by the expression level of the cancer marker of the present invention in blood. Therefore, for example, the biological sample is preferably whole blood, serum, or plasma, and more preferably serum or plasma, because the burden on the patient or doctor can be reduced.
　前記測定工程におけるがんマーカーの発現量の測定は、例えば、前記生体試料における本発明のがんマーカーの有無の分析（定性分析）でもよいし、前記がんマーカーの量の分析（定量分析）でもよい。 The measurement of the expression level of the cancer marker in the measurement step may be, for example, analysis of the presence or absence of the cancer marker of the present invention in the biological sample (qualitative analysis), or analysis of the amount of the cancer marker (quantitative analysis). It may be.
　前記測定工程において測定対象のがんマーカーは、前記本発明のがんマーカーであり、具体的には、抗ＨＩＲＩＰ３抗体、ＨＩＲＩＰ３、抗ＦＮＤＣ１１抗体、ＦＮＤＣ１１、抗ＳＬＣ１Ａ３抗体、ＳＬＣ１Ａ３、抗ＴＭＥＭ３３抗体、ＴＭＥＭ３３、抗ＡＢＣＦ１抗体、ＡＢＣＦ１、抗ＣＦＤＰ１抗体、ＣＦＤＰ１、抗ＰＯＬＲ３ＧＬ抗体、ＰＯＬＲ３ＧＬ、抗ＣＡＤＭ１抗体、ＣＡＤＭ１、抗ＲＮＦ１２８抗体、ＲＮＦ１２８、抗ＡＴＰ６Ｖ１Ｂ１抗体、およびＡＴＰ６Ｖ１Ｂ１からなる群から選択される少なくとも１つである。前記がんマーカーは、例えば、よりマーカーとしての精度が高いことから、抗ヒト由来ＨＩＲＩＰ３抗体、抗ヒト由来ＦＮＤＣ１１抗体、抗ヒト由来ＳＬＣ１Ａ３抗体、および抗ヒト由来ＴＭＥＭ３３抗体からなる群から選択される少なくとも１つの抗体を含むことが好ましく、抗ヒト由来ＨＩＲＩＰ３抗体を含むことがより好ましい。 The cancer marker to be measured in the measurement step is the cancer marker of the present invention, and specifically, anti-HIRIP3 antibody, HIRIP3, anti-FNDC11 antibody, FNDC11, anti-SLC1A3 antibody, SLC1A3, anti-TMEM33 antibody, TMEM33. , Anti-ABCF1 antibody, ABCF1, anti-CFDP1 antibody, CFDP1, anti-POLR3GL antibody, POLR3GL, anti-CADM1 antibody, CADM1, anti-RNF128 antibody, RNF128, anti-ATP6V1B1 antibody, and ATP6V1B1 at least one selected from the group. The cancer marker is selected from the group consisting of an anti-human-derived HIRIP3 antibody, an anti-human-derived FNDC11 antibody, an anti-human-derived SLC1A3 antibody, and an anti-human-derived TMEM33 antibody because of its higher accuracy as a marker, for example. It preferably contains one antibody, more preferably an anti-human derived HIRIP3 antibody.
　前記がんマーカーは、１種類を用いてもよいし、２種類以上を併用してもよい。後者の場合、本発明のがんマーカーの組合せは、特に制限されず、任意のがんマーカーの組合せとできる。具体例として、本発明のがんマーカーの組合せは、よりマーカーとしての精度が高いことから、抗ヒト由来ＨＩＲＩＰ３抗体、抗ヒト由来ＦＮＤＣ１１抗体、抗ヒト由来ＳＬＣ１Ａ３抗体、および抗ヒト由来ＴＭＥＭ３３抗体を含むことが好ましい。 One type of the cancer marker may be used, or two or more types may be used in combination. In the latter case, the combination of cancer markers of the present invention is not particularly limited and can be any combination of cancer markers. As a specific example, the combination of cancer markers of the present invention includes an anti-human-derived HIRIP3 antibody, an anti-human-derived FNDC11 antibody, an anti-human-derived SLC1A3 antibody, and an anti-human-derived TMEM33 antibody because of its higher accuracy as a marker. Is preferable.
　測定対象である前記本発明のがんマーカーの発現は、前記本発明の抗体および／または抗原タンパク質の発現でもよいし、これらの遺伝子のｍＲＮＡの発現でもよい。前記測定工程では、例えば、前記生体試料について、前記抗体および／または抗原タンパク質を測定してもよいし、これらの遺伝子のｍＲＮＡを測定してもよいし、両方を測定してもよい。各種がんマーカーの測定方法は、特に制限されず、公知の方法が採用できる。具体例として、前記ｍＲＮＡ発現の測定方法は、例えば、逆転写（Reverse　transcription：ＲＴ）－ＰＣＲ法等の逆転写反応を利用した遺伝子増幅法等があげられる。具体的には、例えば、ｍＲＮＡから逆転写反応でｃＤＮＡを合成し、前記ｃＤＮＡを鋳型として遺伝子増幅する方法である。また、前記タンパク質発現の測定方法は、例えば、化学発光酵素免疫測定法（CLEIA）等の免疫抗体法、ＥＬＩＳＡ法、フローサイトメトリーおよびウエスタンブロット法等があげられる。 The expression of the cancer marker of the present invention to be measured may be the expression of the antibody and / or antigen protein of the present invention, or the expression of mRNA of these genes. In the measurement step, for example, the antibody and / or the antigen protein may be measured, the mRNA of these genes may be measured, or both may be measured with respect to the biological sample. The method for measuring various cancer markers is not particularly limited, and a known method can be adopted. As a specific example, the method for measuring mRNA expression includes, for example, a gene amplification method using a reverse transcription reaction such as a reverse transcription (RT) -PCR method. Specifically, for example, it is a method of synthesizing cDNA from mRNA by a reverse transcription reaction and amplifying the gene using the cDNA as a template. Examples of the method for measuring protein expression include an immunoantibody method such as chemiluminescent enzyme immunoassay (CLEIA), an ELISA method, flow cytometry, and Western blotting.
　本発明の試験方法は、さらに、前記被検者の生体試料（以下、「被検生体試料」ともいう）における本発明のがんマーカーの発現量を、基準値と比較することにより、前記被検者のがんの罹患危険度を試験する工程（試験工程）を含んでもよい。前記基準値は、特に制限されず、例えば、健常者、がん患者および進行ステージごとのがん患者の本発明のがんマーカーの発現量等があげられる。予後の評価の場合、前記基準値は、例えば、同じ被検者の治療後（例えば、治療直後）の本発明のがんマーカーの発現量であってもよい。 The test method of the present invention further comprises comparing the expression level of the cancer marker of the present invention in the biological sample of the subject (hereinafter, also referred to as “test biological sample”) with a reference value. It may include a step (testing step) of testing the examiner's risk of developing cancer. The reference value is not particularly limited, and examples thereof include the expression level of the cancer marker of the present invention in healthy subjects, cancer patients, and cancer patients at each stage of progression. In the case of evaluation of prognosis, the reference value may be, for example, the expression level of the cancer marker of the present invention after treatment (for example, immediately after treatment) of the same subject.
　前記基準値は、例えば、前述のような、健常者および／またはがん患者から単離した生体試料（以下、「基準生体試料」ともいう）を用いて、得ることができる。また、予後の評価の場合、例えば、同じ被検者から治療後に単離した基準生体試料を用いてもよい。前記基準値は、例えば、前記被検者の被検生体試料と同時に測定してもよいし、予め測定してもよい。後者の場合、例えば、前記被検者の被検生体試料を測定する度に、基準値を得ることが不要となるため、好ましい。前記被検者の被検生体試料と前記基準生体試料は、例えば、同じ条件で採取し、同じ条件で本発明のがんマーカーの測定を行うことが好ましい。 The reference value can be obtained, for example, by using a biological sample (hereinafter, also referred to as "reference biological sample") isolated from a healthy person and / or a cancer patient as described above. Further, in the case of evaluation of prognosis, for example, a reference biological sample isolated after treatment from the same subject may be used. The reference value may be measured at the same time as the test biological sample of the subject, or may be measured in advance. In the latter case, for example, it is not necessary to obtain a reference value every time the test biological sample of the subject is measured, which is preferable. It is preferable that the test biological sample of the subject and the reference biological sample are collected under the same conditions, and the cancer marker of the present invention is measured under the same conditions.
　前記試験工程において、被検者のがんの罹患危険度の評価方法は、特に制限されず、前記基準値の種類によって適宜決定できる。具体例として、前記被検者の被検生体試料における本発明のがんマーカーの発現量が、前記健常者の基準生体試料における本発明のがんマーカーの発現量よりも有意に高い場合、前記がん患者の基準生体試料における本発明のがんマーカーの発現量と同じ場合（有意差がない場合）、および／または、前記がん患者の基準生体試料における本発明のがんマーカーの発現量よりも有意に高い場合、前記被検者は、がんに罹患する危険性があるまたは危険性が高いと評価できる。また、前記被検者の被検生体試料における本発明のがんマーカーの発現量が、前記健常者の基準生体試料における本発明のがんマーカーの発現量と同じ場合（有意差が無い場合）、前記健常者の基準生体試料における本発明のがんマーカーの発現量よりも有意に低い場合、および／または、前記がん患者の基準生体試料における本発明のがんマーカーの発現量よりも有意に低い場合、前記被検者は、がんに罹患する危険性が無いまたは危険性が低いと評価できる。また、前記試験工程において、前記被検者の被検生体試料における本発明のがんマーカーの発現量を、前記進行ステージごとのがん患者の基準生体試料における本発明のがんマーカーの発現量と比較することで、がんの進行度を評価できる。具体的には、前記被検者の被検生体試料が、例えば、いずれかの進行ステージの前記基準生体試料と同程度の発現量の場合（有意差がない場合）、前記被検者は、前記進行ステージの可能性があると評価できる。 In the test step, the method for evaluating the risk of developing cancer in a subject is not particularly limited, and can be appropriately determined depending on the type of the reference value. As a specific example, when the expression level of the cancer marker of the present invention in the test biological sample of the subject is significantly higher than the expression level of the cancer marker of the present invention in the reference biological sample of the healthy subject, the above. When it is the same as the expression level of the cancer marker of the present invention in the reference biological sample of the cancer patient (when there is no significant difference) and / or, the expression level of the cancer marker of the present invention in the reference biological sample of the cancer patient If it is significantly higher than, the subject can be assessed as at risk or at high risk of developing cancer. Further, when the expression level of the cancer marker of the present invention in the test biological sample of the subject is the same as the expression level of the cancer marker of the present invention in the reference biological sample of the healthy subject (when there is no significant difference). , Significantly lower than the expression level of the cancer marker of the present invention in the reference biological sample of the healthy subject, and / or significantly lower than the expression level of the cancer marker of the present invention in the reference biological sample of the cancer patient. If it is low, the subject can be evaluated as having no or low risk of developing cancer. Further, in the test step, the expression level of the cancer marker of the present invention in the test biological sample of the subject is measured by the expression level of the cancer marker of the present invention in the reference biological sample of the cancer patient for each stage of progression. The degree of cancer progression can be evaluated by comparing with. Specifically, when the test biological sample of the test subject has an expression level similar to that of the reference biological sample of any progression stage (when there is no significant difference), the test subject It can be evaluated that there is a possibility of the progress stage.
　前記試験工程において、予後の状態を評価する場合、例えば、前述と同様に評価判断してもよいし、基準値として、同じ被検者の治療後の基準生体試料における本発明のがんマーカーの発現量を使用して評価することもできる。具体例として、前記被検者の被検生体試料における本発明のがんマーカーの発現量が、前記基準値よりも有意に高い場合、前記被検者は、前記治療後、再発または悪化の危険性があると評価できる。また、前記被検者の被検生体試料における本発明のがんマーカーの発現量が、前記基準値と同じ場合（有意差がない場合）、および／または、前記基準値よりも有意に低い場合、前記被検者は、前記治療後、再発の危険性が無いもしくは危険性が低いと評価できる。 When evaluating the prognosis state in the test step, for example, the evaluation may be made in the same manner as described above, or as a reference value, the cancer marker of the present invention in the reference biological sample after treatment of the same subject. It can also be evaluated using the expression level. As a specific example, when the expression level of the cancer marker of the present invention in the test biological sample of the subject is significantly higher than the reference value, the subject is at risk of recurrence or deterioration after the treatment. It can be evaluated as having sex. In addition, when the expression level of the cancer marker of the present invention in the test biological sample of the subject is the same as the reference value (when there is no significant difference) and / or when it is significantly lower than the reference value. The subject can be evaluated as having no risk of recurrence or a low risk of recurrence after the treatment.
　本発明において、例えば、同じ被検者の生体試料を経時的に採取し、前記生体試料における本発明のがんマーカー発現量を比較してもよい。これによって、例えば、経時的に発現量が増加すれば、罹患の可能性が高くなった等の判断が可能であり、経時的に発現量が低下すれば、罹患の可能性が低くなったまたは治癒してきた等の判断が可能である。 In the present invention, for example, a biological sample of the same subject may be collected over time and the expression level of the cancer marker of the present invention in the biological sample may be compared. This makes it possible to determine, for example, that if the expression level increases over time, the possibility of morbidity increases, and if the expression level decreases over time, the possibility of morbidity decreases or It is possible to judge that it has healed.
　本発明の試験方法は、例えば、前記試験工程において、がんに罹患する危険性があるまたは危険性が高いと評価された被検者、治療後に再発または悪化の危険性があると評価された被検者に対し、さらに、がんの治療薬を投与する工程（投与工程）を含んでもよい。この場合、本発明の試験方法は、がんの試験および治療方法ということもできる。 The test method of the present invention was evaluated, for example, in the test process, a subject who was evaluated to have a risk of developing cancer or a high risk of developing cancer, and a subject who was evaluated to have a risk of recurrence or exacerbation after treatment. A step (administration step) of administering a therapeutic agent for cancer to the subject may be further included. In this case, the test method of the present invention can also be said to be a cancer test and treatment method.
　前記がん治療薬は、特に制限されず、前記がんの種類に応じて、適宜決定できる。前記がんが乳がんの場合、前記乳がん治療薬は、例えば、抗ＨＥＲ２抗体、抗ＶＥＧＦ抗体、抗ＲＡＮＫＬ抗体等の分子標的薬、トポイソメラーゼ阻害薬、微小管作用薬、アルキル化薬、代謝拮抗薬、白金錯体、ホルモン剤等があげられる。前記がん治療薬の投与条件（投与対象、投与量、投与形態、投与方法等）は、特に制限されず、前記がんの種類に応じて、適宜決定できる。 The cancer therapeutic agent is not particularly limited and can be appropriately determined according to the type of cancer. When the cancer is breast cancer, the breast cancer therapeutic agent is, for example, a molecular target drug such as an anti-HER2 antibody, an anti-VEGF antibody, an anti-RANKL antibody, a topoisomerase inhibitor, a microtubule agent, an alkylating agent, a metabolic antagonist, Examples include platinum complexes and hormonal agents. The administration conditions (administration target, dose, administration form, administration method, etc.) of the cancer therapeutic agent are not particularly limited and can be appropriately determined according to the type of the cancer.
（がんの試験キット）
　本発明のがんの試験キットは、前述のように、がんマーカーの発現測定試薬を含み、前記がんマーカーが、前記本発明のがんマーカーを含む。本発明の試験キットによれば、前記本発明のがんの罹患危険度の試験方法を簡便に行える。本発明の試験キットは、がんの罹患危険度の試験を本発明のがんマーカーの発現に基づいて行うことが特徴であり、その他の構成および条件は、特に制限されない。本発明の試験キットは、本発明のがんマーカーの発現が測定できればよく、例えば、前記本発明の試験方法に使用できる。本発明の試験キットは、本発明のがんマーカーおよび試験方法の説明を援用できる。 (Cancer test kit)
As described above, the cancer test kit of the present invention contains a reagent for measuring the expression of a cancer marker, and the cancer marker contains the cancer marker of the present invention. According to the test kit of the present invention, the test method for the risk of developing cancer of the present invention can be easily performed. The test kit of the present invention is characterized in that the risk of developing cancer is tested based on the expression of the cancer marker of the present invention, and other configurations and conditions are not particularly limited. The test kit of the present invention only needs to be able to measure the expression of the cancer marker of the present invention, and can be used, for example, in the test method of the present invention. The test kit of the present invention can be referred to the description of the cancer marker and the test method of the present invention.
　前記発現測定試薬の種類は、特に制限されず、例えば、本発明のがんマーカーの種類に応じて適宜設定できる。前記発現測定試薬は、例えば、本発明の抗体および／または抗原タンパク質の発現測定試薬でもよく、これらの遺伝子のｍＲＮＡの発現測定試薬でもよい。 The type of the expression measuring reagent is not particularly limited, and can be appropriately set according to, for example, the type of the cancer marker of the present invention. The expression measuring reagent may be, for example, the expression measuring reagent for the antibody and / or the antigen protein of the present invention, or may be the expression measuring reagent for the mRNA of these genes.
　本発明の試験キットは、例えば、前記がんマーカーの発現測定試薬のみを含んでもよい。前記発現測定試薬の測定対象のがんマーカーは、前述のように、前記本発明のがんマーカーであり、具体的には、抗ＨＩＲＩＰ３抗体、ＨＩＲＩＰ３、抗ＦＮＤＣ１１抗体、ＦＮＤＣ１１、抗ＳＬＣ１Ａ３抗体、ＳＬＣ１Ａ３、抗ＴＭＥＭ３３抗体、ＴＭＥＭ３３、抗ＡＢＣＦ１抗体、ＡＢＣＦ１、抗ＣＦＤＰ１抗体、ＣＦＤＰ１、抗ＰＯＬＲ３ＧＬ抗体、ＰＯＬＲ３ＧＬ、抗ＣＡＤＭ１抗体、ＣＡＤＭ１、抗ＲＮＦ１２８抗体、ＲＮＦ１２８、抗ＡＴＰ６Ｖ１Ｂ１抗体、およびＡＴＰ６Ｖ１Ｂ１からなる群から選択される少なくとも１つである。前記がんマーカーは、例えば、よりマーカーとしての精度が高いことから、抗ヒト由来ＨＩＲＩＰ３抗体、抗ヒト由来ＦＮＤＣ１１抗体、抗ヒト由来ＳＬＣ１Ａ３抗体、および抗ヒト由来ＴＭＥＭ３３抗体からなる群から選択される少なくとも１つの抗体を含むことが好ましく、抗ヒト由来ＨＩＲＩＰ３抗体を含むことがより好ましい。 The test kit of the present invention may contain, for example, only the reagent for measuring the expression of the cancer marker. As described above, the cancer marker to be measured by the expression measuring reagent is the cancer marker of the present invention, and specifically, anti-HIRIP3 antibody, HIRIP3, anti-FNDC11 antibody, FNDC11, anti-SLC1A3 antibody, SLC1A3. , Anti-TMEM33 antibody, TMEM33, anti-ABCF1 antibody, ABCF1, anti-CFDP1 antibody, CFDP1, anti-POLR3GL antibody, POLR3GL, anti-CADM1 antibody, CADM1, anti-RNF128 antibody, RNF128, anti-ATP6V1B1 antibody, and ATP6V1B1. At least one. The cancer marker is selected from the group consisting of an anti-human-derived HIRIP3 antibody, an anti-human-derived FNDC11 antibody, an anti-human-derived SLC1A3 antibody, and an anti-human-derived TMEM33 antibody because of its higher accuracy as a marker, for example. It preferably contains one antibody, more preferably an anti-human derived HIRIP3 antibody.
　前記発現測定試薬の測定対象のがんマーカーは、１種類でもよいし、２種類以上でもよい。後者の場合、前記がんマーカーの組合せは、特に制限されず、任意のがんマーカーの組合せとできる。具体例として、前記がんマーカーの組合せは、よりマーカーとしての精度が高いことから、抗ヒト由来ＨＩＲＩＰ３抗体、抗ヒト由来ＦＮＤＣ１１抗体、抗ヒト由来ＳＬＣ１Ａ３抗体、および抗ヒト由来ＴＭＥＭ３３抗体を含むことが好ましい。 The cancer marker to be measured by the expression measurement reagent may be one type or two or more types. In the latter case, the combination of the cancer markers is not particularly limited and can be any combination of cancer markers. As a specific example, the combination of the cancer markers may include an anti-human-derived HIRIP3 antibody, an anti-human-derived FNDC11 antibody, an anti-human-derived SLC1A3 antibody, and an anti-human-derived TMEM33 antibody because the combination of the cancer markers has higher accuracy as a marker. preferable.
　前記がんマーカーの発現測定試薬の種類は、前記がんマーカーの種類に合わせて適宜設定できる。 The type of the expression measuring reagent for the cancer marker can be appropriately set according to the type of the cancer marker.
　前記がんマーカーが、前記本発明の抗体（抗ＨＩＲＩＰ３抗体、抗ＦＮＤＣ１１抗体、抗ＳＬＣ１Ａ３抗体、抗ＴＭＥＭ３３抗体、抗ＡＢＣＦ１抗体、抗ＣＦＤＰ１抗体、抗ＰＯＬＲ３ＧＬ抗体、抗ＣＡＤＭ１抗体、抗ＲＮＦ１２８抗体、および／または抗ＡＴＰ６Ｖ１Ｂ１抗体）である場合、前記発現測定試薬は、前記本発明の抗体が結合可能な抗原タンパク質またはその部分配列からなるペプチド（前記がんマーカーに対応する抗原）と、前記本発明の抗体を検出可能な検出試薬を含んでもよい。 The cancer markers are the antibodies of the present invention (anti-HIRI P3 antibody, anti-FNDC11 antibody, anti-SLC1A3 antibody, anti-TMEM33 antibody, anti-ABCF1 antibody, anti-CFDP1 antibody, anti-POLR3GL antibody, anti-CADM1 antibody, anti-RNF128 antibody, and / Alternatively, in the case of an anti-ATP6V1B1 antibody), the expression measuring reagent is an antigen protein to which the antibody of the present invention can bind or a peptide consisting of a partial sequence thereof (an antigen corresponding to the cancer marker) and the antibody of the present invention. It may contain a detection reagent capable of detecting.
　この場合、前記検出試薬は、例えば、前記測定方法の種類に応じて、アルカリフォスファターゼ（ＡＬＰ）、ルシフェラーゼ等の酵素；放射性同位元素；粒子、蛍光タンパク質等の蛍光物質；色素物質等の色素；発光物質；電子供与体；酵素の発色基質；ＤＮＰ（ジニトロフェノール）、ＴＮＰ（トリニトロフェノール）等のハプテン、ビオチン等のビタミン類；等の標識で標識化してもよい。前記粒子は、例えば、金、銀等の金属粒子、着色ラテックス粒子等のラテックス粒子、および磁性粒子等があげられる。前記磁性粒子としては、例えば、タンパク質が固相化された固相化磁性粒子があげられ、具体例として、例えば、高ＤＮＰ抗体が固相化された高ＤＮＰ抗体磁性粒子、ストレプトアビジン（ＳｔＡｖｉ）が固相化されたＳｔＡｖｉ固相化磁性粒子等があげられる。また、前記検出試薬は、例えば、前記検出方法の種類に応じて、酵素の基質、二価鉄（Ｆｅ２＋）等の還元剤等と併用してもよい。前記酵素の基質は、特に制限されず、前記酵素に応じて適宜設定できる。具体例として、前記酵素としてＡＬＰを使用する場合、前記酵素の基質は、例えば、CDP-Star（登録商標）、ＮＢＴ等があげられる。 In this case, the detection reagent is, for example, an enzyme such as alkaline phosphatase (ALP) or luciferase; a fluorescent substance such as particles or a fluorescent protein; a dye such as a pigment substance; a luminescence, depending on the type of the measurement method. It may be labeled with a substance; an electron donor; a color-developing substrate of an enzyme; a hapten such as DNP (dinitrophenol) or TNP (trinitrophenol), or a vitamin such as biotin; Examples of the particles include metal particles such as gold and silver, latex particles such as colored latex particles, and magnetic particles. Examples of the magnetic particles include solidified magnetic particles on which a protein is immobilized. Specific examples thereof include high DNP antibody magnetic particles on which a high DNP antibody is immobilized, and streptavidin (StAvi). Examples thereof include StAvi-immobilized magnetic particles on which the substance is immobilized. Further, the detection reagent may be used in combination with, for example, an enzyme substrate, a reducing agent such as ferrous iron (Fe 2+ ), or the like, depending on the type of the detection method. The substrate of the enzyme is not particularly limited and can be appropriately set according to the enzyme. As a specific example, when ALP is used as the enzyme, the substrate of the enzyme includes, for example, CDP-Star (registered trademark), NBT and the like.
　前記本発明の抗体を検出する検出試薬は、例えば、本発明の抗体を認識する抗体であってもよい。前記検出試薬が抗体の場合、例えば、前記本発明の抗体に結合する一次抗体のみを使用してもよいし、前記本発明の抗体に結合する一次抗体と前記一次抗体に結合する二次抗体（結合検出試薬）とを併用してもよい。前者の場合、本発明の試験キットは、例えば、前記本発明の抗体に対する一次抗体の結合を検出することにより、前記本発明の抗体と、前記がんマーカーに対応する抗原と、前記一次抗体との複合体を検出できる。後者の場合、本発明の試験キットは、例えば、前記本発明の抗体に結合した一次抗体に対する二次抗体の結合を検出することにより、前記本発明の抗体と、前記がんマーカーに対応する抗原と、前記一次抗体と、前記二次抗体との複合体を検出できる。前記結合の検出は、例えば、前記抗体の標識を検出することにより実施できる。また、前者の場合、前記一次抗体が、例えば、標識化された標識化抗体であることが好ましい。後者の場合、前記二次抗体が、例えば、標識化された標識化抗体であることが好ましい。 The detection reagent for detecting the antibody of the present invention may be, for example, an antibody that recognizes the antibody of the present invention. When the detection reagent is an antibody, for example, only the primary antibody that binds to the antibody of the present invention may be used, or the primary antibody that binds to the antibody of the present invention and the secondary antibody that binds to the primary antibody ( It may be used in combination with a binding detection reagent). In the former case, the test kit of the present invention comprises, for example, the antibody of the present invention, the antigen corresponding to the cancer marker, and the primary antibody by detecting the binding of the primary antibody to the antibody of the present invention. Complex can be detected. In the latter case, the test kit of the present invention can detect the binding of the secondary antibody to the primary antibody bound to the antibody of the present invention, for example, to detect the antibody of the present invention and the antigen corresponding to the cancer marker. And the complex of the primary antibody and the secondary antibody can be detected. The detection of the binding can be carried out, for example, by detecting the label of the antibody. In the former case, the primary antibody is preferably, for example, a labeled labeled antibody. In the latter case, the secondary antibody is preferably, for example, a labeled labeled antibody.
　前記がんマーカーに対応する抗原タンパク質またはその部分配列からなるペプチドは、遊離した状態で使用してもよいし、担体に担持された状態（固定化した状態）で使用してもよい。後者の場合、前記抗原は、例えば、前記その他の成分として前記担体を含む。前記担体は、特に制限されず、例えば、ウェルプレート等のプレート、ビーズ、多孔質体、多孔質膜、フィルタ等のメンブレン等があげられる。前記固定化は、直接的な固定化でもよいし、間接的な固定化でもよい。 The antigen protein corresponding to the cancer marker or a peptide consisting of a partial sequence thereof may be used in a free state or in a carrier-supported state (immobilized state). In the latter case, the antigen comprises, for example, the carrier as the other component. The carrier is not particularly limited, and examples thereof include plates such as well plates, beads, porous bodies, porous membranes, and membranes such as filters. The immobilization may be direct immobilization or indirect immobilization.
　具体例として、本発明の試験キット（以下、「第１のキット」ともいう）は、例えば、第１の標識および第２の標識で標識化されたがんマーカーに対応する抗原タンパク質またはその部分配列を含む第１の試薬と、前記第１の標識に結合可能な抗体が担体に固定化された第２の試薬と、本発明の抗体に結合可能な抗体（前記一次抗体）が第３の標識で標識化された第３の試薬と、前記第１の標識を含む第４の試薬と、前記第２の標識に結合可能な結合物質が担体に固定化された第５の試薬と、前記第３の標識と反応し、シグナルを発する基質を含む第６の試薬とを含む。前記第１のキットにおいて、前記第１の標識は、好ましくは、ＤＮＰ、ＴＮＰ等のハプテンであり、より好ましくは、ＤＮＰである。前記第２の標識は、好ましくは、ビオチンである。前記第３の標識は、好ましくは、ＡＬＰである。前記第２の試薬における担体は、好ましくは、磁性担体である。前記第４の試薬は、好ましくは、前記第１の標識で標識化された標識物質を含み、より好ましくは、ＤＮＰで標識化されたリジンを含む。前記第２の標識に結合可能な結合物質は、好ましくは、ストレプトアビジンである。前記第５の試薬における担体は、好ましくは、磁性担体である。前記第６の試薬における基質は、好ましくは、ＡＬＰの基質である。 As a specific example, the test kit of the present invention (hereinafter, also referred to as “first kit”) is, for example, an antigen protein or a portion thereof corresponding to a cancer marker labeled with a first label and a second label. A first reagent containing a sequence, a second reagent in which an antibody capable of binding to the first label is immobilized on a carrier, and an antibody capable of binding to the antibody of the present invention (the primary antibody) are third. A third reagent labeled with a label, a fourth reagent containing the first label, a fifth reagent in which a binding substance capable of binding to the second label is immobilized on a carrier, and the above. It contains a sixth reagent containing a substrate that reacts with the third label and emits a signal. In the first kit, the first label is preferably a hapten such as DNP or TNP, and more preferably DNP. The second label is preferably biotin. The third label is preferably ALP. The carrier in the second reagent is preferably a magnetic carrier. The fourth reagent preferably comprises a labeling substance labeled with the first label, and more preferably contains a DNP-labeled lysine. The binding agent capable of binding to the second label is preferably streptavidin. The carrier in the fifth reagent is preferably a magnetic carrier. The substrate in the sixth reagent is preferably a substrate for ALP.
　つぎに、前記第２の試薬および前記第５の試薬における担体が磁性担体である場合を例にあげて、前記第１のキットを用いた、前記本発明の抗体を検出方法について説明する。ただし、以下の説明は、前記第１のキットを用いた本発明の抗体の検出方法の一例であり、前記第１のキットの使用法は、以下の説明に限定されない。 Next, a method for detecting the antibody of the present invention using the first kit will be described by taking as an example the case where the carrier in the second reagent and the fifth reagent is a magnetic carrier. However, the following description is an example of the antibody detection method of the present invention using the first kit, and the usage of the first kit is not limited to the following description.
　まず、被検者の生体試料と、前記第１の試薬と前記第２の試薬と前記第３の試薬とを接触させ、前記被検者の生体試料に由来する本発明の抗体と、前記第１の試薬と、前記第２の試薬と、前記第３の試薬との複合体（第１の複合体）を形成する（第１の複合体形成工程）。具体的には、本発明の抗体に対して、前記第１の試薬における抗体および前記第３の試薬の抗体が結合し、さらに、前記第１の試薬における抗体の第１の標識に対して、前記第２の試薬の抗体が結合する。これにより、前記第１の複合体形成工程において、前記第１の複合体を形成できる。 First, the biological sample of the subject is brought into contact with the first reagent, the second reagent, and the third reagent, and the antibody of the present invention derived from the biological sample of the subject and the second reagent. A complex (first complex) of the first reagent, the second reagent, and the third reagent is formed (first complex forming step). Specifically, the antibody in the first reagent and the antibody in the third reagent bind to the antibody of the present invention, and further, with respect to the first label of the antibody in the first reagent. The antibody of the second reagent binds. As a result, the first complex can be formed in the first complex forming step.
　つぎに、得られた混合物を磁性体に結合させることで、前記第１の複合体を含む固体画分と、それ以外の液体画分とを固液分離し、前記液体画分を除去する（第１の固液分離工程）。前記第１の固液分離工程後、前記固体画分は、例えば、洗浄液で洗浄してもよい。さらに、前記固体画分を、前記第４の試薬と接触させ、前記第１の複合体から、前記被検者の生体試料に由来する本発明の抗体と、前記第１の試薬と、前記第３の試薬との複合体（第２の複合体）を遊離させる（遊離工程）。前記第２の複合体は、前記第２の試薬における抗体の結合部位に対して、前記第１の試薬における第１の標識と、前記第４の試薬における第１の標識とが競合することにより生じる。前記遊離工程において、添加される前記第４の試薬における第１の標識の分子数は、例えば、前記第１の試薬における第１の標識の分子数より多いことが好ましく、過剰量であることがより好ましい。 Next, by binding the obtained mixture to a magnetic material, the solid fraction containing the first complex and the other liquid fractions are solid-liquid separated, and the liquid fraction is removed ( First solid-liquid separation step). After the first solid-liquid separation step, the solid fraction may be washed with, for example, a washing liquid. Further, the solid fraction is brought into contact with the fourth reagent, and from the first complex, the antibody of the present invention derived from the biological sample of the subject, the first reagent, and the first reagent. The complex (second complex) with the reagent of 3 is released (free step). The second complex is produced by competing the first label in the first reagent and the first label in the fourth reagent with respect to the binding site of the antibody in the second reagent. Occurs. In the release step, the number of molecules of the first label added in the fourth reagent is preferably larger than the number of molecules of the first label in the first reagent, and is preferably an excess amount. More preferred.
　つぎに、得られた混合物を磁性体に結合させることで、前記第２の複合体を含む液体画分と、それ以外の固体画分とを固液分離し、前記液体画分を回収する（第２の固液分離工程）。さらに、前記液体画分を前記第５の試薬と接触させ、前記被検者の生体試料に由来する本発明の抗体と、前記第１の試薬と、前記第３の試薬と、前記第５の試薬との複合体（第３の複合体）を形成する（第２の複合体形成工程）。前記第３の複合体は、前記第２の複合体における前記第２の標識に対して、前記第５の試薬における結合物質が結合することで形成できる。 Next, by binding the obtained mixture to a magnetic material, the liquid fraction containing the second complex and the other solid fractions are solid-liquid separated, and the liquid fraction is recovered ( Second solid-liquid separation step). Further, the liquid fraction is brought into contact with the fifth reagent, and the antibody of the present invention derived from the biological sample of the subject, the first reagent, the third reagent, and the fifth reagent are used. A complex (third complex) with the reagent is formed (second complex forming step). The third complex can be formed by binding the binding substance in the fifth reagent to the second label in the second complex.
　そして、得られた混合物を磁性体に結合させることで、前記第３の複合体を含む固体画分と、それ以外の液体画分とを固液分離し、前記液体画分を除去する（第３の固液分離工程）。前記第３の固液分離工程後、前記固体画分は、例えば、洗浄液で洗浄してもよい。さらに、前記固体画分を、前記第６の試薬と接触させ、前記第３の複合体における第３の標識と、前記基質とを反応させ、得られたシグナルを検出する（検出工程）。そして、前記シグナルに基づき、前記本発明の抗体の有無または量を検出する。 Then, by binding the obtained mixture to the magnetic material, the solid fraction containing the third complex and the other liquid fractions are solid-liquid separated, and the liquid fraction is removed (the first). 3 solid-liquid separation step). After the third solid-liquid separation step, the solid fraction may be washed with, for example, a washing liquid. Further, the solid fraction is brought into contact with the sixth reagent, the third label in the third complex is reacted with the substrate, and the obtained signal is detected (detection step). Then, based on the signal, the presence or absence or amount of the antibody of the present invention is detected.
　前記がんマーカーが、前記本発明の抗原タンパク質（ＨＩＲＩＰ３、ＦＮＤＣ１１、ＳＬＣ１Ａ３、ＴＭＥＭ３３、ＡＢＣＦ１、ＣＦＤＰ１、ＰＯＬＲ３ＧＬ、ＣＡＤＭ１、ＲＮＦ１２８、および／またはＡＴＰ６Ｖ１Ｂ１）である場合、例えば、前記発現測定試薬は、前記抗原タンパク質に結合する物質、および前記抗原タンパク質と前記結合物質の結合を検出する検出試薬を含んでもよい。 When the cancer marker is the antigen protein of the present invention (HIRIP3, FNDC11, SLC1A3, TMEM33, ABCF1, CFDP1, POLR3GL, CADM1, RNF128, and / or ATP6V1B1), for example, the expression measuring reagent is the antigen. A substance that binds to a protein and a detection reagent that detects the binding between the antigen protein and the binding substance may be included.
　前記がんマーカーに結合する物質は、前記がんマーカーに結合する物質であれば特に制限されず、例えば、前記がんマーカーを認識する抗体、アプタマー等があげられる。前記がんマーカーを認識する抗体またはアプタマーは、例えば、前記標識化されていてもよい。前記標識化は、前述の説明を援用できる。 The substance that binds to the cancer marker is not particularly limited as long as it is a substance that binds to the cancer marker, and examples thereof include antibodies and aptamers that recognize the cancer marker. The antibody or aptamer that recognizes the cancer marker may be, for example, labeled. The above-mentioned description can be used for the labeling.
　前記検出試薬が抗体の場合、例えば、前記抗原タンパク質に結合する一次抗体のみを使用してもよいし、前記抗原タンパク質に結合する一次抗体と前記一次抗体に結合する二次抗体（結合検出試薬）とを併用してもよい。前者の場合、前記試験キットは、例えば、前記抗原タンパク質に対する一次抗体の結合を検出することにより、前記本発明の抗原タンパク質と前記一次抗体との複合体を検出できる。後者の場合、前記試験キットは、例えば、前記抗原タンパク質に結合した一次抗体に対する二次抗体の結合を検出することにより、前記抗原タンパク質と、前記一次抗体と、前記二次抗体との複合体を検出できる。前記結合の検出は、例えば、前記抗体の標識を検出することにより実施できる。また、前者の場合、前記一次抗体が、例えば、標識化された標識化抗体であることが好ましい。後者の場合、前記二次抗体が、例えば、標識化された標識化抗体であることが好ましい。 When the detection reagent is an antibody, for example, only the primary antibody that binds to the antigen protein may be used, or the primary antibody that binds to the antigen protein and the secondary antibody that binds to the primary antibody (binding detection reagent). May be used in combination with. In the former case, the test kit can detect a complex of the antigen protein of the present invention and the primary antibody, for example, by detecting the binding of the primary antibody to the antigen protein. In the latter case, the test kit comprises a complex of the antigen protein, the primary antibody, and the secondary antibody, for example, by detecting the binding of the secondary antibody to the primary antibody bound to the antigen protein. Can be detected. The detection of the binding can be carried out, for example, by detecting the label of the antibody. In the former case, the primary antibody is preferably, for example, a labeled labeled antibody. In the latter case, the secondary antibody is preferably, for example, a labeled labeled antibody.
　前記がんマーカーが、前記本発明の抗体および／または抗原タンパク質の遺伝子である場合、例えば、前記発現測定試薬は、前記ｍＲＮＡの逆転写試薬および前記ｍＲＮＡから逆転写されたｃＤＮＡの増幅試薬を含んでもよいし、前記ｍＲＮＡの塩基配列を解読するシークエンス試薬を含んでもよい。前者の場合、具体例として、前記発現測定試薬は、例えば、プライマーがあげられる。前記プライマーは、例えば、本発明のがんマーカーの遺伝子配列に基づいて適宜設計できる。 When the cancer marker is a gene for the antibody and / or antigen protein of the present invention, for example, the expression measuring reagent includes a reverse transcription reagent of the mRNA and an amplification reagent of the cDNA reverse transcribed from the mRNA. Alternatively, it may contain a sequence reagent for decoding the base sequence of the mRNA. In the former case, as a specific example, the expression measuring reagent includes, for example, a primer. The primer can be appropriately designed based on, for example, the gene sequence of the cancer marker of the present invention.
　具体例として、本発明の試験キット（以下、「第２のキット」ともいう）は、例えば、第１の標識および第２の標識で標識化された本発明の抗原タンパク質に結合可能な抗体を含む第１の試薬と、前記第１の標識に結合可能な抗体が担体に固定化された第２の試薬と、本発明の抗原タンパク質に結合可能な抗体（前記一次抗体）が第３の標識で標識化された第３の試薬と、前記第１の標識を含む第４の試薬と、前記第２の標識に結合可能な結合物質が担体に固定化された第５の試薬と、前記第３の標識と反応し、シグナルを発する基質を含む第６の試薬とを含む。前記第１のキットにおいて、前記第１の標識は、好ましくは、ＤＮＰ、ＴＮＰ等のハプテンであり、より好ましくは、ＤＮＰである。前記第２の標識は、好ましくは、ビオチンである。前記第３の標識は、好ましくは、ＡＬＰである。前記第２の試薬における担体は、好ましくは、磁性担体である。前記第４の試薬は、好ましくは、前記第１の標識で標識化された標識物質を含み、より好ましくは、ＤＮＰで標識化されたリジンを含む。前記第２の標識に結合可能な結合物質は、好ましくは、ストレプトアビジンである。前記第５の試薬における担体は、好ましくは、磁性担体である。前記第６の試薬における基質は、好ましくは、ＡＬＰの基質である。前記第２のキットは、例えば、前記第１のキットと同様にして使用できる。 As a specific example, the test kit of the present invention (hereinafter, also referred to as “second kit”) contains, for example, an antibody capable of binding to the antigen protein of the present invention labeled with the first label and the second label. A first reagent containing, a second reagent in which an antibody capable of binding to the first label is immobilized on a carrier, and an antibody capable of binding to the antigen protein of the present invention (the primary antibody) are labeled as a third. A third reagent labeled with, a fourth reagent containing the first label, a fifth reagent in which a binding substance capable of binding to the second label is immobilized on a carrier, and the second reagent. Includes a sixth reagent containing a substrate that reacts with the label of 3 and emits a signal. In the first kit, the first label is preferably a hapten such as DNP or TNP, and more preferably DNP. The second label is preferably biotin. The third label is preferably ALP. The carrier in the second reagent is preferably a magnetic carrier. The fourth reagent preferably comprises a labeling substance labeled with the first label, and more preferably contains a DNP-labeled lysine. The binding agent capable of binding to the second label is preferably streptavidin. The carrier in the fifth reagent is preferably a magnetic carrier. The substrate in the sixth reagent is preferably a substrate for ALP. The second kit can be used, for example, in the same manner as the first kit.
　本発明の試験キットは、例えば、さらに、その他の構成要素を含んでもよい。前記構成要素は、例えば、前記担体、前記酵素の基質、緩衝液、洗浄液、および磁性粒子と抗体との遊離剤等の試薬、使用説明書等があげられる。前記遊離剤は、例えば、ジニトロフェニル-リジン（DNP-Lys）等があげられる。本発明の試験キットにおける各試薬は、それぞれ、別個の容器に収容されてもよいし、同一の容器に混合または未混合で収容されてもよい。後者の場合、本発明の試験キットは、試験試薬ということもできる。本発明の試験キットが前記基質を含む場合、前記基質は、例えば、前記担体および前記検出試薬と別個の容器に収容されている。 The test kit of the present invention may further include, for example, other components. Examples of the component include the carrier, the substrate of the enzyme, a buffer solution, a washing solution, reagents such as a release agent between magnetic particles and an antibody, and instructions for use. Examples of the liberating agent include dinitrophenyl-lysine (DNP-Lys) and the like. Each reagent in the test kit of the present invention may be contained in a separate container, or may be contained in the same container mixed or unmixed. In the latter case, the test kit of the present invention can also be referred to as a test reagent. When the test kit of the present invention contains the substrate, the substrate is contained, for example, in a container separate from the carrier and the detection reagent.
　本発明の試験キットにおいて、前記試験対象のがんは、特に制限されず、例えば、前記本発明のがんマーカーおよび試験方法の記載を援用できる。前記試験対象のがんは、乳がんが好ましい。 In the test kit of the present invention, the cancer to be tested is not particularly limited, and for example, the description of the cancer marker and the test method of the present invention can be incorporated. Breast cancer is preferable as the cancer to be tested.
（がんマーカーの測定方法）
　本発明のがんマーカーの測定方法は、前述のように、被検者の生体試料と、がんマーカーの発現測定試薬とを接触させ、前記生体試料におけるがんマーカーの発現量を測定する工程を含み、前記がんマーカーが、前記本発明のがんマーカーを含む。本発明の測定方法は、被験者の生体試料と、がんマーカーの発現測定試薬とを接触させ、前記生体試料におけるがんマーカーの発現量を測定する工程を含むことが特徴であり、その他の工程および条件は、特に制限されない。本発明の測定方法は、前記本発明のがんマーカー、試験方法および、試験キットの説明を援用できる。 (Measurement method of cancer marker)
As described above, the method for measuring a cancer marker of the present invention is a step of bringing a biological sample of a subject into contact with a cancer marker expression measuring reagent and measuring the expression level of the cancer marker in the biological sample. The cancer marker comprises the cancer marker of the present invention. The measuring method of the present invention is characterized by including a step of contacting a biological sample of a subject with a reagent for measuring the expression of a cancer marker and measuring the expression level of the cancer marker in the biological sample, and other steps. And the conditions are not particularly limited. As the measuring method of the present invention, the description of the cancer marker, the test method, and the test kit of the present invention can be incorporated.
（がん治療薬の候補物質のスクリーニング方法）
　本発明のスクリーニング方法は、がん治療薬候補物質のスクリーニング方法であって、被検物質から、がんマーカーの発現を抑制する発現抑制物質を、前記治療用候補物質として選択する工程を含み、前記がんマーカーが、前記本発明のがんマーカーを含む。本発明は、前記選択工程において、前記本発明のがんマーカーに基づき、前記治療薬候補物質を選択することが特徴であり、その他の工程および条件は、特に制限されない。本発明のスクリーニング方法は、前記本発明のがんマーカー、試験方法、試験キット、および測定方法の説明を援用できる。 (Screening method for candidate substances for cancer treatment)
The screening method of the present invention is a screening method for a candidate substance for a cancer therapeutic drug, and includes a step of selecting an expression-suppressing substance that suppresses the expression of a cancer marker from a test substance as the candidate substance for treatment. The cancer marker includes the cancer marker of the present invention. The present invention is characterized in that the therapeutic drug candidate substance is selected based on the cancer marker of the present invention in the selection step, and other steps and conditions are not particularly limited. The screening method of the present invention can be referred to the description of the cancer marker, the test method, the test kit, and the measurement method of the present invention.
　前記発現抑制物質は、例えば、前記がんマーカー遺伝子からのｍＲＮＡの転写を抑制する物質、転写されたｍＲＮＡを切断する物質およびｍＲＮＡからのタンパク質の翻訳を抑制する物質等があげられる。具体例としては、例えば、ｓｉＲＮＡ等のＲＮＡ干渉剤、アンチセンス、リボザイム等があげられる。 Examples of the expression-suppressing substance include a substance that suppresses transcription of mRNA from the cancer marker gene, a substance that cleaves the transcribed mRNA, and a substance that suppresses translation of protein from mRNA. Specific examples include RNA interfering agents such as siRNA, antisense, and ribozymes.
　前記被験物質は、特に制限されず、例えば、低分子化合物、ペプチド、タンパク質および核酸からなる群から選択された少なくとも１つである。 The test substance is not particularly limited, and is, for example, at least one selected from the group consisting of low molecular weight compounds, peptides, proteins and nucleic acids.
　本発明の前記発現抑制物質のスクリーニング方法は、例えば、本発明がんマーカーの発現系に前記被検物質を共存させて、本発明のがんマーカーを発現させる工程（発現工程）と、前記発現系における本発明のがんマーカーの発現を検出する工程（検出工程）と、本発明のがんマーカーの発現量が、前記被検物質を共存させていないコントロールの発現系よりも低い前記被検物質を、前記治療用候補物質として選択する工程とを含む。前記検出工程において、検出対象の前記発現は、例えば、本発明のがんマーカータンパク質の発現でもよいし、本発明のがんマーカー遺伝子のｍＲＮＡの転写でもよい。前記タンパク質の発現およびｍＲＮＡの発現の検出方法は、特に制限されず、前述の説明を援用できる。 The method for screening the expression-suppressing substance of the present invention includes, for example, a step (expression step) in which the test substance is allowed to coexist in the expression system of the cancer marker of the present invention to express the cancer marker of the present invention, and the expression thereof. The step of detecting the expression of the cancer marker of the present invention in the system (detection step) and the test in which the expression level of the cancer marker of the present invention is lower than that of the control expression system in which the test substance does not coexist. It includes a step of selecting a substance as a candidate substance for treatment. In the detection step, the expression to be detected may be, for example, expression of the cancer marker protein of the present invention or transcription of mRNA of the cancer marker gene of the present invention. The method for detecting the expression of the protein and the expression of mRNA is not particularly limited, and the above description can be incorporated.
　前記がんマーカーが、抗ＨＩＲＩＰ３抗体、抗ＦＮＤＣ１１抗体、抗ＳＬＣ１Ａ３抗体、抗ＴＭＥＭ３３抗体、抗ＡＢＣＦ１抗体、抗ＣＦＤＰ１抗体、抗ＰＯＬＲ３ＧＬ抗体、抗ＣＡＤＭ１抗体、抗ＲＮＦ１２８抗体、および抗ＡＴＰ６Ｖ１Ｂ１抗体からなる群から選択される少なくとも１つの抗体である場合、本発明のスクリーニング方法は、例えば、前記被検物質を生体に投与する工程（投与工程）と、前記生体において、前記がんマーカーを発現させる工程（発現工程）と、前記投与後の生体から生体試料を取得する工程と、前記生体試料におけるがんマーカーの発現を測定する工程と、前記生体試料におけるがんマーカーの発現量が、前記被検物質を投与していないコントロール由来の生体試料よりも低い前記被検物質を、前記治療用候補物質として選択する工程とを含む。前記投与工程において前記生体に投与する被検物質の投与条件は、前記被検物質の種類に応じて、適宜設定できる。前記生体は、例えば、ヒト、ヒトを除く非ヒト動物等があげられ、前記非ヒト動物は、例えば、マウス、ラット、イヌ、サル、ウサギ、ヒツジ、ウマ等の哺乳類があげられる。前記発現工程において前記がんマーカーの発現は、例えば、前記がんマーカーに対応するタンパク質を前記生体に免疫することにより実施できる。前記取得工程において、前記生体試料は、例えば、前記血液試料があげられる。 The cancer marker consists of a group consisting of anti-HIRI P3 antibody, anti-FNDC11 antibody, anti-SLC1A3 antibody, anti-TMEM33 antibody, anti-ABCF1 antibody, anti-CFDP1 antibody, anti-POLR3GL antibody, anti-CADM1 antibody, anti-RNF128 antibody, and anti-ATP6V1B1 antibody. When it is at least one antibody to be selected, the screening method of the present invention is, for example, a step of administering the test substance to a living body (administration step) and a step of expressing the cancer marker in the living body (expression). Step), the step of obtaining a biological sample from the living body after the administration, the step of measuring the expression of the cancer marker in the biological sample, and the expression level of the cancer marker in the biological sample are the same as the test substance. It includes a step of selecting the test substance, which is lower than the biological sample derived from the control not administered, as the therapeutic candidate substance. The administration conditions of the test substance to be administered to the living body in the administration step can be appropriately set according to the type of the test substance. Examples of the living body include humans and non-human animals other than humans, and examples of the non-human animals include mammals such as mice, rats, dogs, monkeys, rabbits, sheep and horses. In the expression step, the expression of the cancer marker can be carried out, for example, by immunizing the living body with a protein corresponding to the cancer marker. In the acquisition step, examples of the biological sample include the blood sample.
　前記がんマーカーは、ＨＩＲＩＰ３、ＦＮＤＣ１１、ＳＬＣ１Ａ３、ＴＭＥＭ３３、ＡＢＣＦ１、ＣＦＤＰ１、ＰＯＬＲ３ＧＬ、ＣＡＤＭ１、ＲＮＦ１２８、およびＡＴＰ６Ｖ１Ｂ１からなる群から選択される少なくとも１つのがんマーカーのタンパク質または遺伝子である場合、本発明のスクリーニング方法は、例えば、前記がんマーカーの発現系に前記被検物質を共存させて、がんマーカーを発現させる工程、前記発現系におけるがんマーカーの発現を検出する工程と、前記がんマーカーの発現量が、前記被検物質を共存させていないコントロールの発現系よりも低い前記被検物質を、前記治療用候補物質として選択する工程とを含む。 When the cancer marker is a protein or gene of at least one cancer marker selected from the group consisting of HIRIP3, FNDC11, SLC1A3, TMEM33, ABCF1, CFDP1, POLR3GL, CADM1, RNF128, and ATP6V1B1, the present invention. The screening method includes, for example, a step of coexisting the test substance in the expression system of the cancer marker to express the cancer marker, a step of detecting the expression of the cancer marker in the expression system, and the cancer marker. The expression level of the test substance is lower than that of the control expression system in which the test substance does not coexist, and the step of selecting the test substance as the therapeutic candidate substance is included.
　つぎに、本発明の実施例について説明する。ただし、本発明は、下記実施例により制限されない。 Next, examples of the present invention will be described. However, the present invention is not limited by the following examples.
［実施例１］
　乳がん患者および健常者の血清中において、本発明の抗体（本発明のがんマーカーに対する自己抗体）の抗体価を測定した。 [Example 1]
The antibody titer of the antibody of the present invention (autoantibody against the cancer marker of the present invention) was measured in the sera of breast cancer patients and healthy subjects.
（自己抗原の調製）
　自己抗原タンパク質として、ＨＩＲＩＰ３、ＦＮＤＣ１１、ＳＬＣ１Ａ３、ＴＭＥＭ３３、ＡＢＣＦ１、ＣＦＤＰ１、ＰＯＬＲ３ＧＬ、ＣＡＤＭ１、ＲＮＦ１２８、および、ＡＴＰ６Ｖ１Ｂ１を、コムギ無細胞タンパク質合成系を用いて合成した。前記コムギ無細胞タンパク質合成は、下記参考文献１に記載の方法に従って行った。なお、前記各自己抗原タンパク質のＤＮＡ鋳型には、あらかじめアミノ末端にＨｉｓタグおよびｂｌｓタグをコードする配列を付加した。そして、下記参考文献２に記載の方法により、前記無細胞合成時に、反応系にビオチンリガーゼ(BirA）およびD-ビオチンを加え、前記自己抗原タンパク質に付加したｂｌｓタグのリジン残基をビオチン化しながら合成した。また、比較例として、乳がんマーカーであるＴＰ５３（ｐ５３）を、同様にして合成した。
参考文献1：Takai, K et.al.,. “Practical cell-free protein synthesis system using purified wheat embryos.” Nat Protoc. 2010, volume 5, pages 227-238
参考文献２：Sawasaki, Tet.al. “Arabidopsis HY5 protein functions as a DNA-binding tag for purification and functional immobilization of proteins on agarose/DNA microplate.”, FEBS Letters, 2008, volume 582, pages 221-228 (Preparation of self-antigen)
As self-antigen proteins, HIRIP3, FNDC11, SLC1A3, TMEM33, ABCF1, CFDP1, POLR3GL, CADM1, RNF128, and ATP6V1B1 were synthesized using a wheat cell-free protein synthesis system. The wheat cell-free protein synthesis was carried out according to the method described in Reference 1 below. In addition, a sequence encoding a His tag and a bls tag was added to the amino terminus in advance to the DNA template of each self-antigen protein. Then, biotin ligase (BirA) and D-biotin were added to the reaction system during the cell-free synthesis by the method described in Reference 2 below, and the lysine residue of the bls tag added to the self-antigen protein was biotinylated. Synthesized. In addition, as a comparative example, TP53 (p53), which is a breast cancer marker, was synthesized in the same manner.
Reference 1: Takai, K et.al. ,. “Practical cell-free protein synthesis system using purified wheat embryos.” Nat Protoc. 2010, volume 5, pages 227-238
Reference 2: Sawasaki, Tet.al. “Arabidopsis HY5 protein functions as a DNA-binding tag for purification and functional immobilization of proteins on agarose / DNA microplate.”, FEBS Letters, 2008, volume 582, pages 221-228
　血清試料として、未治療の乳がん患者女性（ｎ＝６８３）および健常者女性（ｎ＝３０、対照群）から文書により同意を得た上で採血し、血液から血清を回収した。そして、血清中の抗体価を、下記参考文献３および４に記載の方法に従い、Alpha（Amplified Luminescent Proximity Homogeneous Assay）Screen法により測定した。具体的には、まず、未修飾AlphaScreen アクセプタービーズ（PerkinElmer社）に、Protein Gをアミンカップリングを用いて共有結合させ、Protein G修飾アクセプタービーズを作成した。そして、前記無細胞合成した前記ビオチン化自己抗原タンパク質０．４μＬと、血清試料０．０２５μＬを、２０μＬの希釈液（100 mmol/L Tris-HCl, pH8.0、0.01% Tween20、1 mg/mL ウシ血清アルブミン）中で混和し、室温（２５℃）で３０分間静置し、反応液を調製した。その後、AlphaScreen Protein G修飾アクセプタービーズ０．０６μＬとAlphaScreenストレプトアビジン修飾ドナービーズ（PerkinElmer社）０．０６μＬとを含む希釈液（100 mmol/L Tris-HCl, pH8.0、0.01% Tween20、1 mg/mL ウシ血清アルブミン）５μＬを、前記反応液に添加し、さらに室温で６０分静置した。そして、前記反応液中の抗原―抗体反応を、Ｅｎｖｉｓｉｏｎのプレートリーダー（PerkinElmer社）を用いて検出した。コントロールは、各自己抗原タンパク質を添加しなかった以外は同様にして検出した。そして、各マーカーのシグナル強度について、コントロールのシグナル強度との比を算出した。この結果を図１に示す。
参考文献３：Ishigami, T et.al., “Anti-interleukin-5 and multiple autoantibodies are associated with human atherosclerotic diseases and serum interleukin-5 levels.”, The FASEB Journal, 2013, volume 27, pages3437-3445
参考文献４：Onishi, S. et.al., “Novel Autoantigens Associated with Lupus Nephritis.”, PLoS ONE, 2015, volume 10, page e0126564 As serum samples, blood was collected from untreated breast cancer patient women (n = 683) and healthy women (n = 30, control group) with written consent, and serum was collected from the blood. Then, the antibody titer in serum was measured by the Alpha (Amplified Luminescent Proximity Homogeneous Assay) Screen method according to the methods described in References 3 and 4 below. Specifically, first, Protein G was covalently bonded to unmodified AlphaScreen acceptor beads (PerkinElmer) using an amine coupling to prepare Protein G-modified acceptor beads. Then, 0.4 μL of the cell-free synthesized biotinylated autoantigen protein and 0.025 μL of the serum sample were added to a 20 μL diluted solution (100 mmol / L Tris-HCl, pH8.0, 0.01% Tween20, 1 mg / mL). It was mixed in bovine serum albumin) and allowed to stand at room temperature (25 ° C.) for 30 minutes to prepare a reaction solution. Then, a diluent (100 mmol / L Tris-HCl, pH8.0, 0.01% Tween20, 1 mg) containing 0.06 μL of AlphaScreen Protein G-modified acceptor beads and 0.06 μL of AlphaScreen streptavidin-modified donor beads (PerkinElmer) / mL Bovine serum albumin) 5 μL was added to the reaction solution, and the mixture was allowed to stand at room temperature for 60 minutes. Then, the antigen-antibody reaction in the reaction solution was detected using an Envision plate reader (PerkinElmer). Controls were detected in the same manner except that each autoantigen protein was not added. Then, the ratio of the signal intensity of each marker to the signal intensity of the control was calculated. The result is shown in FIG.
Reference 3: Ishigami, T et.al., “Anti-interleukin-5 and multiple autoantibodies are associated with human atherosclerotic diseases and serum interleukin-5 levels.”, The FASEB Journal, 2013, volume 27, pages 3437-3445
Reference 4: Onishi, S. et.al., “Novel Autoantigens Associated with Lupus Nephritis.”, PLoS ONE, 2015, volume 10, page e0126564
　図１は、各抗原の抗体価を示すグラフであり、（Ａ）は、グラフの全体図であり、（Ｂ）は、（Ａ）の対応するグラフの縦軸を拡大した図である。図１の各グラフにおいて、縦軸は、AlphaScreenのシグナル強度（抗体価）を示し、左側が健常者、右側が乳がん患者の血清試料の結果を示す。図１に示すように、乳がん患者は、健常者と比較して、血清中のＨＩＲＩＰ３、ＦＮＤＣ１１、ＳＬＣ１Ａ３、ＴＭＥＭ３３、ＡＢＣＦ１、ＣＦＤＰ１、ＰＯＬＲ３ＧＬ、ＣＡＤＭ１、ＲＮＦ１２８、および、ＡＴＰ６Ｖ１Ｂ１に対する自己抗体のシグナル強度が有意に高かった。中でも、ＨＩＲＩＰ３、ＦＮＤＣ１１、ＳＬＣ１Ａ３、およびＴＭＥＭ３３に対する自己抗体のシグナル強度が特に高く、乳がんマーカーであるＴＰ５３に対する自己抗体と比較して、乳がん患者／健常者の抗体価シグナル比が高く、乳がんマーカーとしてｐ５３と比較して好適に使用できることがわかった。これらのことから、本発明のがんマーカーが、乳がんのマーカーとなることがわかった。 FIG. 1 is a graph showing the antibody titer of each antigen, (A) is an overall view of the graph, and (B) is an enlarged view of the vertical axis of the corresponding graph of (A). In each graph of FIG. 1, the vertical axis shows the signal intensity (antibody titer) of AlphaScreen, the left side shows the results of serum samples of healthy subjects, and the right side shows the results of serum samples of breast cancer patients. As shown in FIG. 1, breast cancer patients have significant signal intensities of autoantibodies to serum HIRIP3, FNDC11, SLC1A3, TMEM33, ABCF1, CFDP1, POLR3GL, CADM1, RNF128, and ATP6V1B1 as compared to healthy subjects. It was expensive. Among them, the signal intensity of autoantibodies against HIRIP3, FNDC11, SLC1A3, and TMEM33 is particularly high, and the antibody titer signal ratio of breast cancer patients / healthy subjects is higher than that of autoantibodies against TP53, which is a breast cancer marker, and p53 as a breast cancer marker. It was found that it can be used favorably in comparison with. From these facts, it was found that the cancer marker of the present invention serves as a marker for breast cancer.
［実施例２］
　乳がんのステージによる、本発明の抗体（本発明のがんマーカーに対する自己抗体）の抗体価の変化を確認した。 [Example 2]
Changes in the antibody titer of the antibody of the present invention (autoantibody against the cancer marker of the present invention) depending on the stage of breast cancer were confirmed.
　前記実施例１で抗体価シグナル比が高かった４種のがんマーカー（抗ＨＩＲＩＰ３抗体、抗ＦＮＤＣ１１抗体、抗ＳＬＣ１Ａ３抗体、および抗ＴＭＥＭ３３抗体）および比較例（抗ＴＰ５３抗体）について、乳がん患者のステージを０期（ｎ＝９７）、Ｉ期（ｎ＝２７０）、II期（ｎ＝２５４）、III期（ｎ＝３４）に分けた以外は前記実施例１と同様にして、血清中の抗体価を確認した。なお、乳がんのステージ分類を下記表１および図２に示す。
Figure JPOXMLDOC01-appb-T000001
 The stages of breast cancer patients with respect to the four cancer markers (anti-HIRI P3 antibody, anti-FNDC11 antibody, anti-SLC1A3 antibody, and anti-TMEM33 antibody) and comparative example (anti-TP53 antibody) having high antibody titer signal ratios in Example 1 The antibody in serum was the same as in Example 1 except that the antibody was divided into stage 0 (n = 97), stage I (n = 270), stage II (n = 254), and stage III (n = 34). I confirmed the value. The stage classification of breast cancer is shown in Table 1 and FIG. 2 below.
Figure JPOXMLDOC01-appb-T000001
　図２は、各ステージにおける各抗原に対する抗体価を示すグラフである。図２において、上段は、グラフ全体を示し、下段は、上段のグラフの縦軸を拡大した図である。図２の各グラフにおいて、縦軸は、AlphaScreenのシグナル強度（抗体価）を示し、横軸は、左から、対照群、０期、Ｉ期、II期、III期の血清サンプルを示す。図２に示すように、ＨＩＲＩＰ３、ＦＮＤＣ１１、ＳＬＣ１Ａ３、およびＴＭＥＭ３３に対する自己抗体は、いずれのステージの乳がんであっても高いシグナルを示した。また、ＴＰ５３に対する自己抗体と比較して、０期の乳がんにおける抗体価が高かった。これらのことから、本発明のがんマーカーは、乳がんの早期診断マーカーとして使用可能であることがわかった。前述のように、０期の乳がんは、しこりや画像診断での異常な影等がみられず、早期発見が困難であるが、本発明のがんマーカーによれば、例えば、乳がんの早期診断が可能となる。 FIG. 2 is a graph showing the antibody titer against each antigen at each stage. In FIG. 2, the upper part shows the entire graph, and the lower part is an enlarged view of the vertical axis of the upper graph. In each graph of FIG. 2, the vertical axis shows the signal intensity (antibody titer) of AlphaScreen, and the horizontal axis shows the control group, stage 0, stage I, stage II, and stage III serum samples from the left. As shown in FIG. 2, autoantibodies to HIRIP3, FNDC11, SLC1A3, and TMEM33 showed high signaling in any stage of breast cancer. In addition, the antibody titer in stage 0 breast cancer was higher than that of autoantibodies against TP53. From these facts, it was found that the cancer marker of the present invention can be used as an early diagnostic marker for breast cancer. As described above, stage 0 breast cancer is difficult to detect early because no lumps or abnormal shadows are observed in diagnostic imaging. However, according to the cancer marker of the present invention, for example, early diagnosis of breast cancer Is possible.
［実施例３］
　乳がんのサブタイプと、本発明の抗体（本発明のがんマーカーに対する自己抗体）抗体価との関係を確認した。 [Example 3]
The relationship between the subtype of breast cancer and the antibody titer of the antibody of the present invention (autoantibody against the cancer marker of the present invention) was confirmed.
　前記実施例１で高い抗体価を示した４種のがんマーカー（抗ＨＩＲＩＰ３抗体、抗ＦＮＤＣ１１抗体、抗ＳＬＣ１Ａ３抗体、および抗ＴＭＥＭ３３抗体）について、乳がんのサブタイプをＬｕｍｉｎａｌ　Ａ（ｎ＝４１１）、Ｌｕｍｉｎａｌ　Ｂ（ｎ＝３８）、Ｈｅｒ２（ｎ＝４１）、およびＴｒｉｐｌｅ　ｎｅｇａｔｉｖｅ（ｎ＝５８）に分けた以外は前記実施例１と同様にして、血清中の抗体価を確認した。この結果を図３に示す。 For the four cancer markers (anti-HIRI P3 antibody, anti-FNDC11 antibody, anti-SLC1A3 antibody, and anti-TMEM33 antibody) that showed high antibody titers in Example 1, the subtype of breast cancer was Luminal A (n = 411). The antibody titer in serum was confirmed in the same manner as in Example 1 except that it was divided into Luminal B (n = 38), Her2 (n = 41), and Triple negative (n = 58). The result is shown in FIG.
　図３は、各乳がんのサブタイプにおける各抗原に対する抗体価を示す。図３において、上段は、グラフ全体を示し、下段は、上段のグラフの縦軸を拡大した図である。図３の各グラフにおいて、縦軸は、AlphaScreenのシグナル強度（抗体価）を示し、横軸は、左から、対照群、Ｌｕｍｉｎａｌ　Ａ（Ａ）、Ｌｕｍｉｎａｌ　Ｂ（Ｂ）、Ｈｅｒ２（Ｈ）、およびＴｒｉｐｌｅ　ｎｅｇａｔｉｖｅ（Ｔ）の血清サンプルを示す。図３に示すように、ＨＩＲＩＰ３、ＦＮＤＣ１１、ＳＬＣ１Ａ３、およびＴＭＥＭ３３に対する自己抗体は、いずれのサブタイプの乳がんにおいても、高いシグナルを示し、発現していることが確認できた。また、いずれのサブタイプの乳がんにおいても、乳がんマーカーであるＴＰ５３に対する自己抗体と比較して、乳がん患者／健常者の抗体価シグナル比が高く、好適に使用できることがわかった。これらのことから、本発明のがんマーカーは、乳がんのサブタイプによらず使用できることがわかった。 FIG. 3 shows the antibody titer against each antigen in each breast cancer subtype. In FIG. 3, the upper part shows the entire graph, and the lower part is an enlarged view of the vertical axis of the upper graph. In each graph of FIG. 3, the vertical axis shows the signal intensity (antibody titer) of AlphaScreen, and the horizontal axis shows the control group, Luminal A (A), Luminal B (B), Her2 (H), and Her2 (H) from the left. A serum sample of Triple negative (T) is shown. As shown in FIG. 3, it was confirmed that autoantibodies against HIRIP3, FNDC11, SLC1A3, and TMEM33 showed high signals and were expressed in all subtypes of breast cancer. In addition, it was found that in all subtypes of breast cancer, the antibody titer signal ratio of breast cancer patients / healthy subjects was higher than that of autoantibodies against TP53, which is a breast cancer marker, and it can be preferably used. From these facts, it was found that the cancer marker of the present invention can be used regardless of the subtype of breast cancer.
［実施例４］
　組織免疫染色により、本発明のがんマーカーであるＨＩＲＩＰ３が乳がん組織で発現していることを確認した。 [Example 4]
Tissue immunostaining confirmed that the cancer marker of the present invention, HIRIP3, was expressed in breast cancer tissue.
　神奈川県立がんセンター病理診断科で保管する、患者４０名分の、ホルマリン固定パラフィン包埋された乳がん組織から切片を作製し、脱パラフィン操作、再水和操作を行い、被検サンプルを作成した。そして、前記被検サンプルについて、クエン酸緩衝液（ｐＨ６）中に浸漬した状態で、高圧蒸気滅菌器で１５分間処理し、抗原性の賦活化を行った。前記賦活化後、リン酸緩衝液(PBS)で洗浄し、続いて、３％過酸化水素水に５分間浸漬して、内在性ペルオキシダーゼを不活性化し、リン酸緩衝生理食塩水（ＰＢＳ）で洗浄した。 Sections were prepared from breast cancer tissue embedded in formalin-fixed paraffin for 40 patients stored at the Department of Pathology, Kanagawa Cancer Center, and deparaffinized and rehydrated to prepare test samples. .. Then, the test sample was treated with a high-pressure steam sterilizer for 15 minutes in a state of being immersed in a citric acid buffer (pH 6) to activate the antigenicity. After the activation, it is washed with phosphate buffer (PBS) and then immersed in 3% hydrogen peroxide solution for 5 minutes to inactivate endogenous peroxidase and with phosphate buffered saline (PBS). It was washed.
　前記被検サンプルを、１７００倍希釈した抗ラビットＨＩＲＩＰ３ポリクローナル抗体（Sigma-Aldrich、 HPA063205）と、室温で１時間反応させ、前記ＰＢＳで洗浄した。つぎに、前記被検サンプルを、ＨＲＰ標識２次抗体「ヒストファイン　シンプルステインMAX-PO(MULTI)」（ニチレイバイオサイエンス、724152）と、室温で３０分間反応させた。続いて、前記被検サンプルを前記ＰＢＳで洗浄し、「ＤＡＢ基質キット」（ニチレイバイオサイエンス、725191）で発色させた。そして、前記被検サンプルを流水で洗浄し、ヘマトキシリンで核染色をした。前記染色後の前記被検サンプルを流水で洗浄し、９９．５％エタノールおよび１００％キシレンで脱水および透徹した。その後、前記被検サンプルをマリノールで封入し、ＤＡＢにより茶色に染色されるＨＩＲＩＰ３の発現領域を、光学顕微鏡（BX53、オリンパス社製）を用いて観察した。 The test sample was reacted with a 1700-fold diluted anti-rabbit HIRIP3 polyclonal antibody (Sigma-Aldrich, HPA063205) for 1 hour at room temperature, and washed with the PBS. Next, the test sample was reacted with the HRP-labeled secondary antibody "Histfine Simple Stain MAX-PO (MULTI)" (Nichirei Bioscience, 724152) for 30 minutes at room temperature. Subsequently, the test sample was washed with the PBS and colored with the "DAB Substrate Kit" (Nichirei Bioscience, 725191). Then, the test sample was washed with running water and nuclear-stained with hematoxylin. After the staining, the test sample was washed with running water, dehydrated and cleared with 99.5% ethanol and 100% xylene. Then, the test sample was sealed with marinol, and the expression region of HIRIP3 stained brown by DAB was observed using an optical microscope (BX53, manufactured by Olympus Corporation).
　乳がん組織におけるＨＩＲＩＰ３の発現の結果を図４に示す。図４は、乳がん組織におけるＨＩＲＩＰ３の発現を示す組織染色図であり、（Ａ）は、がんの中心部（Tumor Center Area）を示し、（Ｂ）は、がんの浸潤先端（Tumor Invasion Front）を示す。また、図４（Ｂ）において、矢印で示す、線で囲った領域ががん細胞が存在する領域である。図４において、上段の図は、ＨＥ染色した組織の染色図であり、下段の図は、ＤＡＢ染色した染色図である。図４に示すように、ＨＩＲＩＰ３は、乳がん組織の核に局在した。また、図４（Ｂ）の下段の図に示すように、正常組織は、乳がん組織と比較してＨＩＲＩＰ３の発現量が少ないことがわかった。 The results of HIRIP3 expression in breast cancer tissue are shown in FIG. FIG. 4 is a tissue staining diagram showing the expression of HIRIP3 in breast cancer tissue, (A) shows the central part of the cancer (Tumor Center Area), and (B) shows the infiltration tip of the cancer (Tumor Invasion Front). ) Is shown. Further, in FIG. 4B, the region surrounded by the line indicated by the arrow is the region where the cancer cells are present. In FIG. 4, the upper diagram is a stained diagram of the HE-stained tissue, and the lower diagram is a DAB-stained stained diagram. As shown in FIG. 4, HIRIP3 was localized in the nucleus of breast cancer tissue. Further, as shown in the lower figure of FIG. 4 (B), it was found that the expression level of HIRIP3 was lower in the normal tissue than in the breast cancer tissue.
［実施例５］
　組織免疫染色により、本発明のがんマーカーが様々ながん組織で発現していることを確認した。 [Example 5]
Tissue immunostaining confirmed that the cancer marker of the present invention was expressed in various cancer tissues.
　神奈川県がんセンターが保有するホルマリン固定パラフィン包埋組織の組織アレイを用い、被検サンプルを、乳がん（転移巣または原発巣）、肺がん、および卵巣がんとした以外は、実施例４と同様にして、免疫染色を行った。そして、各被検サンプルにおいて、染色部位の面積が５％以上の場合を免疫染色陽性（ＩＨＣ＋）、染色部位の面積が５％未満の場合を免疫染色陰性（ＩＨＣ－）として検体数を計数し、検体数に対するＩＨＣ＋の割合を算出した。 Same as Example 4 except that the tissue array of formalin-fixed paraffin-embedded tissue owned by the Kanagawa Cancer Center was used and the test samples were breast cancer (metastasis or primary lesion), lung cancer, and ovarian cancer. Then, immunostaining was performed. Then, in each test sample, the number of samples was counted as immunostaining positive (IHC +) when the area of the staining site was 5% or more and immunostaining negative (IHC-) when the area of the staining site was less than 5%. , The ratio of IHC + to the number of samples was calculated.
　この結果を図５に示す。図５は、各被検サンプルにおいて、がんの種類ごとのＩＨＣ＋の割合を示すグラフである。各図５に示すように、ＨＩＲＩＰ３は、乳がん（転移巣）では６６％、乳がん（原発巣）では４１％、肺がんでは２０％、卵巣がんでは２３％発現が確認できた。これらのことから、ＨＩＲＩＰ３は、乳がん、肺がん、および卵巣がんのがんマーカーとして使用できることがわかった。また、乳がんの転移巣において特にＩＨＣ＋の割合が高いことから、乳がんの転移巣のがんマーカーとして好適に使用できることがわかった。 This result is shown in Fig. 5. FIG. 5 is a graph showing the ratio of IHC + for each type of cancer in each test sample. As shown in each FIG. 5, HIRIP3 was confirmed to be expressed in 66% in breast cancer (metastasis), 41% in breast cancer (primary lesion), 20% in lung cancer, and 23% in ovarian cancer. From these facts, it was found that HIRIP3 can be used as a cancer marker for breast cancer, lung cancer, and ovarian cancer. In addition, since the proportion of IHC + is particularly high in the metastatic lesions of breast cancer, it was found that it can be suitably used as a cancer marker for metastatic lesions of breast cancer.
［実施例６］
　組織免疫染色により、本発明のがんマーカーであるＳＬＣ１Ａ３が乳がん組織で発現していることを確認した。 [Example 6]
Tissue immunostaining confirmed that the cancer marker of the present invention, SLC1A3, was expressed in breast cancer tissue.
　被検サンプルを乳がん組織および正常乳腺とし、前記被検サンプルに反応する抗体を抗ラビットＳＬＣ１Ａ３ポリクローナル抗体（abcam、ab41751）し、抗体の希釈倍率を５０倍とした以外は実施例４と同様にして、ＳＬＣ１Ａ３の発現領域を、光学顕微鏡を用いて観察した。 The test sample was breast cancer tissue and normal mammary gland, the antibody reacting with the test sample was an anti-rabbit SLC1A3 polyclonal antibody (abcam, ab41751), and the antibody dilution ratio was set to 50 times in the same manner as in Example 4. , The expression region of SLC1A3 was observed using an optical microscope.
　乳がん組織におけるＳＬＣ１Ａ３の発現の結果を図６に示す。図６は、正常乳腺および乳がん組織におけるＳＬＣ１Ａ３の発現を示す組織染色図であり、左から、乳がん組織のＨＥ染色図、乳がん組織のＤＡＢ染色図、正常乳腺のＤＡＢ染色図である。また、図６において、矢印で示す線で囲った領域が、ＳＬＣ１Ａ３が発現する領域である。図６の上段および下段の図は、異なる検体を使用した以外は同様の図である。図６に示すように、ＳＬＣ１Ａ３は、正常乳腺に比べ、乳がん組織においてより多く発現していることがわかった。 The result of expression of SLC1A3 in breast cancer tissue is shown in FIG. FIG. 6 is a tissue staining diagram showing the expression of SLC1A3 in normal mammary gland and breast cancer tissue, and from the left, HE staining diagram of breast cancer tissue, DAB staining diagram of breast cancer tissue, and DAB staining diagram of normal mammary gland. Further, in FIG. 6, the region surrounded by the line indicated by the arrow is the region where SLC1A3 is expressed. The upper and lower figures of FIG. 6 are similar except that different samples are used. As shown in FIG. 6, SLC1A3 was found to be more expressed in breast cancer tissues than in normal mammary glands.
［実施例７］
　乳がん患者および健常者の血清中において、本発明の抗体（本発明のがんマーカーに対する自己抗体）の抗体価を測定した。 [Example 7]
The antibody titer of the antibody of the present invention (autoantibody against the cancer marker of the present invention) was measured in the sera of breast cancer patients and healthy subjects.
　自己抗原タンパク質として、ＦＮＤＣ１１、ＳＬＣ１Ａ３、ＨＩＲＩＰ３、およびＴＭＥＭ３３とし、サンプル数を、乳がん患者（ｎ＝８３５）および健常者（ｎ＝６６５）とした以外は実施例１と同様にして、乳がん患者および健常者の血清中における、本発明の抗体（本発明のマーカーに対する自己抗体）の抗体価を測定した。また、抗体価の分布を確認したところ、正規分布していなかったため、乳がん患者および健常者の年齢を考慮し、これによる影響を補正した平均値を算出し、共分散分析（ＡＮＣＯＶＡ）により平均値の比較を行なった。なお、以下の各実施例において、同様の統計処理を行なっている。この結果を図７に示す。 The autoantigen proteins were FNDC11, SLC1A3, HIRIP3, and TMEM33, and the number of samples was the same as in Example 1 except that the number of samples was breast cancer patient (n = 835) and healthy subject (n = 665). The antibody titer of the antibody of the present invention (autoantibody against the marker of the present invention) was measured in the serum of the patient. In addition, when the distribution of antibody titers was confirmed, they were not normally distributed. Therefore, considering the ages of breast cancer patients and healthy subjects, the average value corrected for the effect of this was calculated, and the average value was calculated by analysis of covariance (ANCOVA). Was compared. In each of the following examples, the same statistical processing is performed. The result is shown in FIG.
　図７は、各抗原の抗体価を示すグラフである。図７の各グラフにおいて、縦軸は、AlphaScreenのシグナル強度（抗体価）を示し、左側が健常者（対照群）、右側が乳がん患者（患者群）の血清試料の結果を示す。図７に示すように、乳がん患者は、健常者と比較して、血清中のＦＮＤＣ１１、ＳＬＣ１Ａ３、ＨＩＲＩＰ３、およびＴＭＥＭ３３に対する自己抗体のシグナル強度が有意に高く（p < 0.0001）、乳がんマーカーとして好適に使用できることがわかった。これらのことから、本発明のがんマーカーが、乳がんのマーカーとなることがわかった。 FIG. 7 is a graph showing the antibody titer of each antigen. In each graph of FIG. 7, the vertical axis shows the signal intensity (antibody titer) of AlphaScreen, the left side shows the results of serum samples of healthy subjects (control group), and the right side shows the results of serum samples of breast cancer patients (patient group). As shown in FIG. 7, breast cancer patients have significantly higher signal intensities of autoantibodies to FNDC11, SLC1A3, HIRIP3, and TMEM33 in serum than healthy subjects (p <0.0001), and are suitable as breast cancer markers. It turns out that it can be used. From these facts, it was found that the cancer marker of the present invention serves as a marker for breast cancer.
　つぎに、各自己抗原タンパク質に対する抗体価について、ＲＯＣ解析を行ない、感度、特異度、およびＲＯＣ曲線下面積（AUC: area under the curve）を算出することにより、乳がんの診断能を評価した。結果を下記表２に示す。 Next, the antibody titer against each autoantigen protein was subjected to ROC analysis, and the sensitivity, specificity, and area under the ROC curve (AUC: area under the curve) were calculated to evaluate the diagnostic ability of breast cancer. The results are shown in Table 2 below.
Figure JPOXMLDOC01-appb-T000002
Figure JPOXMLDOC01-appb-T000002
　前記表２に示すように、ＦＮＤＣ１１、ＳＬＣ１Ａ３、ＨＩＲＩＰ３、およびＴＭＥＭ３３に対する自己抗体によれば、いずれも高い感度で乳がんを検出できることがわかった。中でも、ＦＮＤＣ１１およびＴＭＥＭ３３に対する自己抗体は、ＡＵＣが、それぞれ、０．９０２および０．８７３であり、極めて高い診断能を有していることがわかった。 As shown in Table 2 above, it was found that all of the autoantibodies against FNDC11, SLC1A3, HIRIP3, and TMEM33 can detect breast cancer with high sensitivity. Among them, the autoantibodies against FNDC11 and TMEM33 were found to have extremely high diagnostic ability with AUC of 0.902 and 0.873, respectively.
［実施例８］
　乳がんのステージによる、本発明の抗体（本発明のがんマーカーに対する自己抗体）の抗体価の変化を確認した。 [Example 8]
Changes in the antibody titer of the antibody of the present invention (autoantibody against the cancer marker of the present invention) depending on the stage of breast cancer were confirmed.
　実施例７で使用したサンプルを使用した以外は、実施例２と同様にして、乳がんのステージによる、本発明のがんマーカーの抗体価の変化を確認した。本実施例において、乳がん患者のステージは、０期（ｎ＝９９）、Ｉ期（ｎ＝３０４）、II期（ｎ＝３１０）、III期（ｎ＝７０）に分け、血清中の抗体価を確認した。なお、乳がん患者（ｎ＝８３５）のうち、ステージ不明であった５２名については、本実施例の結果から除外している。この結果を図８に示す。 The change in the antibody titer of the cancer marker of the present invention was confirmed depending on the stage of breast cancer in the same manner as in Example 2 except that the sample used in Example 7 was used. In this example, the stages of breast cancer patients are divided into stage 0 (n = 99), stage I (n = 304), stage II (n = 310), and stage III (n = 70), and the antibody titer in serum. It was confirmed. Of the breast cancer patients (n = 835), 52 patients whose stage was unknown were excluded from the results of this example. The result is shown in FIG.
　図８は、各ステージにおける各抗原に対する抗体価を示すグラフである。図８の各グラフにおいて、縦軸は、AlphaScreenのシグナル強度（抗体価）を示し、横軸は、左から、対照群、０期、Ｉ期、II期、III期の血清サンプルを示す。図８に示すように、ＦＮＤＣ１１、ＳＬＣ１Ａ３、ＨＩＲＩＰ３、およびＴＭＥＭ３３に対する自己抗体は、いずれのステージの乳がんであっても高いシグナルを示した。これらのことから、本発明のがんマーカーは、乳がんの早期診断マーカーとして使用可能であることがわかった。前述のように、０期の乳がんは、しこりや画像診断での異常な影等がみられず、早期発見が困難であるが、本発明のがんマーカーによれば、例えば、乳がんの早期診断が可能となる。 FIG. 8 is a graph showing the antibody titer against each antigen at each stage. In each graph of FIG. 8, the vertical axis shows the signal intensity (antibody titer) of AlphaScreen, and the horizontal axis shows the control group, stage 0, stage I, stage II, and stage III serum samples from the left. As shown in FIG. 8, autoantibodies to FNDC11, SLC1A3, HIRIP3, and TMEM33 showed high signaling in any stage of breast cancer. From these facts, it was found that the cancer marker of the present invention can be used as an early diagnostic marker for breast cancer. As described above, stage 0 breast cancer is difficult to detect early because no lumps or abnormal shadows are observed in diagnostic imaging. However, according to the cancer marker of the present invention, for example, early diagnosis of breast cancer Is possible.
［実施例９］
　乳がんのサブタイプと、本発明の抗体（本発明のがんマーカーに対する自己抗体）の抗体価の関係を確認した。 [Example 9]
The relationship between the subtype of breast cancer and the antibody titer of the antibody of the present invention (autoantibody against the cancer marker of the present invention) was confirmed.
　実施例７で使用したサンプルを使用した以外は、実施例３と同様にして、乳がんのサブタイプと、本発明のがんマーカーの抗体価の関係を確認した。本実施例において、乳がんのサブタイプは、Ｈｅｒ２（ｎ＝４０）Ｌｕｍｉｎａｌ　Ａ（ｎ＝４０６）、Ｌｕｍｉｎａｌ　Ｂ（ｎ＝３７）、およびＴｒｉｐｌｅ　ｎｅｇａｔｉｖｅ（ｎ＝５６）に分け、血清中の抗体価を確認した。なお、Ｌｕｍｉｎａｌ　ＡまたはＬｕｍｉｎａｌ　Ｂの中間群（Ｌ＊、ｎ＝１０２）および複数のサブタイプが診断された群については、本実施例から除外した。この結果を図９に示す。 The relationship between the breast cancer subtype and the antibody titer of the cancer marker of the present invention was confirmed in the same manner as in Example 3 except that the sample used in Example 7 was used. In this example, the subtypes of breast cancer are divided into Her2 (n = 40) Luminal A (n = 406), Luminal B (n = 37), and Triple negative (n = 56), and the antibody titer in serum is determined. confirmed. The intermediate group (L *, n = 102) of Luminal A or Luminal B and the group diagnosed with a plurality of subtypes were excluded from this example. The result is shown in FIG.
　図９は、各乳がんのサブタイプにおける各抗原に対する抗体価を示す。図９の各グラフにおいて、縦軸は、AlphaScreenのシグナル強度（抗体価）を示し、横軸は、左から、対照群、Ｈｅｒ２、Ｌｕｍｉｎａｌ　Ａ、Ｌｕｍｉｎａｌ　Ｂ、およびＴｒｉｐｌｅ　ｎｅｇａｔｉｖｅの血清サンプルを示す。図９に示すように、ＦＮＤＣ１１、ＳＬＣ１Ａ３、ＨＩＲＩＰ３、およびＴＭＥＭ３３に対する自己抗体は、いずれのサブタイプの乳がんにおいても、高いシグナルを示し、発現していることが確認できた。これらのことから、本発明のがんマーカーは、乳がんのサブタイプによらず使用できることがわかった。 FIG. 9 shows the antibody titer against each antigen in each breast cancer subtype. In each graph of FIG. 9, the vertical axis shows the signal intensity (antibody titer) of AlphaScreen, and the horizontal axis shows the serum samples of the control group, Her2, Luminal A, Luminal B, and Triple negative from the left. As shown in FIG. 9, it was confirmed that autoantibodies to FNDC11, SLC1A3, HIRIP3, and TMEM33 showed high signals and were expressed in all subtypes of breast cancer. From these facts, it was found that the cancer marker of the present invention can be used regardless of the subtype of breast cancer.
　つぎに、各サブタイプにおける、自己抗原タンパク質に対する抗体価について、ＲＯＣ解析を行ない、感度、特異度、およびＲＯＣ曲線下面積（AUC: area under the curve）を算出することにより、サブタイプごとの診断能を評価した。結果を下記表３～６に示す。 Next, the antibody titer against the self-antigen protein in each subtype is diagnosed for each subtype by performing ROC analysis and calculating the sensitivity, specificity, and area under the ROC curve (AUC: area under the curve). I evaluated the ability. The results are shown in Tables 3 to 6 below.
Figure JPOXMLDOC01-appb-T000003
Figure JPOXMLDOC01-appb-T000003
Figure JPOXMLDOC01-appb-T000004
Figure JPOXMLDOC01-appb-T000004
Figure JPOXMLDOC01-appb-T000005
Figure JPOXMLDOC01-appb-T000005
Figure JPOXMLDOC01-appb-T000006
Figure JPOXMLDOC01-appb-T000006
　前記表３～６に示すように、ＦＮＤＣ１１、ＳＬＣ１Ａ３、ＨＩＲＩＰ３、およびＴＭＥＭ３３に対する自己抗体は、いずれも高い感度で、各サブタイプの乳がんを検出できることがわかった。中でも、ＦＮＤＣ１１に対する自己抗体は、各サブタイプにおけるＡＵＣが０．８７７～０．８９７、ＴＭＥＭ３３に対する自己抗体は、各サブタイプにおけるＡＵＣが、０．８６１～０．８８２であり、いずれのサブタイプの乳がんに対しても極めて高い診断能を有していることがわかった。 As shown in Tables 3 to 6, it was found that autoantibodies against FNDC11, SLC1A3, HIRIP3, and TMEM33 can all detect each subtype of breast cancer with high sensitivity. Among them, the autoantibody against FNDC11 has an AUC of 0.877 to 0.897 in each subtype, and the autoantibody against TMEM33 has an AUC of 0.861 to 0.882 in each subtype. It was found that it has extremely high diagnostic ability for breast cancer.
［実施例１０］
　初発の乳がんと、再発の乳がんとで、本発明の（本発明のがんマーカーに対する自己抗体）の関係を確認した。 [Example 10]
The relationship of the present invention (autoantibody against the cancer marker of the present invention) was confirmed between the initial breast cancer and the recurrent breast cancer.
　実施例７の乳がん患者を、初発の患者（ｎ＝８１４）と、再発の患者（ｎ＝２１）に分けた以外は前記実施例７と同様にして、血清中の抗体価を確認した。結果を下記表７に示す。 The antibody titer in serum was confirmed in the same manner as in Example 7 except that the breast cancer patients of Example 7 were divided into first-onset patients (n = 814) and recurrent patients (n = 21). The results are shown in Table 7 below.
Figure JPOXMLDOC01-appb-T000007
Figure JPOXMLDOC01-appb-T000007
　前記表７に示すように、ＦＮＤＣ１１、ＳＬＣ１Ａ３、ＨＩＲＩＰ３、およびＴＭＥＭ３３に対する自己抗体は、初発の乳がんと、再発の乳がんとの間で、抗体価に有意な差はなかった。このため、本発明のがんマーカーは、初発の乳がんおよび再発の乳がんのいずれに対しても診断マーカーとして使用可能であることがわかった。既存の乳がんマーカーの多くは、初発の乳がんの検出には不向きであり、初発の乳がんを検出可能な既存の乳がんマーカーであるＴＰ５３は、乳がん以外のがんを検出してしまうことが知られている。したがって、本発明のがんマーカーによれば、例えば、初発の乳がんの早期診断が可能となる。 As shown in Table 7 above, the autoantibodies against FNDC11, SLC1A3, HIRIP3, and TMEM33 did not have a significant difference in antibody titer between the initial breast cancer and the recurrent breast cancer. Therefore, it was found that the cancer marker of the present invention can be used as a diagnostic marker for both initial breast cancer and recurrent breast cancer. Many of the existing breast cancer markers are not suitable for detecting the first breast cancer, and it is known that TP53, which is an existing breast cancer marker capable of detecting the first breast cancer, detects cancers other than breast cancer. There is. Therefore, according to the cancer marker of the present invention, for example, early diagnosis of initial breast cancer becomes possible.
　以上、実施形態および実施例を参照して本発明を説明したが、本発明は、上記実施形態および実施例に限定されるものではない。本発明の構成や詳細には、本発明のスコープ内で当業者が理解しうる様々な変更をすることができる。 Although the present invention has been described above with reference to the embodiments and examples, the present invention is not limited to the above embodiments and examples. Various changes that can be understood by those skilled in the art can be made to the structure and details of the present invention within the scope of the present invention.
　この出願は、２０１９年３月１１日に出願された日本出願特願２０１９－０４４３１６を基礎とする優先権を主張し、その開示のすべてをここに取り込む。 This application claims priority based on Japanese application Japanese Patent Application No. 2019-044316 filed on March 11, 2019, and incorporates all of its disclosures herein.
＜付記＞
　上記の実施形態および実施例の一部または全部は、以下の付記のように記載されうるが、以下には限られない。
（付記１）
抗ＨＩＲＩＰ３抗体、ＨＩＲＩＰ３、抗ＦＮＤＣ１１抗体、ＦＮＤＣ１１、抗ＳＬＣ１Ａ３抗体、ＳＬＣ１Ａ３、抗ＴＭＥＭ３３抗体、ＴＭＥＭ３３、抗ＡＢＣＦ１抗体、ＡＢＣＦ１、抗ＣＦＤＰ１抗体、ＣＦＤＰ１、抗ＰＯＬＲ３ＧＬ抗体、ＰＯＬＲ３ＧＬ、抗ＣＡＤＭ１抗体、ＣＡＤＭ１、抗ＲＮＦ１２８抗体、ＲＮＦ１２８、抗ＡＴＰ６Ｖ１Ｂ１抗体、およびＡＴＰ６Ｖ１Ｂ１からなる群から選択される少なくとも１つを含む、がんマーカー。
（付記２）
抗ヒト由来ＨＩＲＩＰ３抗体、抗ヒト由来ＦＮＤＣ１１抗体、抗ヒト由来ＳＬＣ１Ａ３抗体、抗ヒト由来ＴＭＥＭ３３抗体、抗ヒト由来ＡＢＣＦ１抗体、抗ヒト由来ＣＦＤＰ１抗体、抗ヒト由来ＰＯＬＲ３ＧＬ抗体、抗ヒト由来ＣＡＤＭ１抗体、抗ヒト由来ＲＮＦ１２８抗体、および抗ヒト由来ＡＴＰ６Ｖ１Ｂ１抗体からなる群から選択される少なくとも１つの抗体を含む、付記１記載のがんマーカー。
（付記３）
抗ヒト由来ＨＩＲＩＰ３抗体、抗ヒト由来ＦＮＤＣ１１抗体、抗ヒト由来ＳＬＣ１Ａ３抗体、および抗ヒト由来ＴＭＥＭ３３抗体からなる群から選択される少なくとも１つの抗体を含む、付記１または２記載のがんマーカー。
（付記４）
前記がんは、乳がん、卵巣がん、膵がん、肝臓がん、胆管がん、大腸がん、結腸がん、直腸がん、胃がん、口腔がん、および肺がんからなる群から選択される少なくとも１つのがんである、付記１から３のいずれかに記載のがんマーカー。
（付記５）
前記がんは、乳がんである、付記１から４のいずれかに記載のがんマーカー。
（付記６）
被検者の生体試料におけるがんマーカーの発現量を測定する工程を含み、
前記がんマーカーは、抗ＨＩＲＩＰ３抗体、ＨＩＲＩＰ３、抗ＦＮＤＣ１１抗体、ＦＮＤＣ１１、抗ＳＬＣ１Ａ３抗体、ＳＬＣ１Ａ３、抗ＴＭＥＭ３３抗体、ＴＭＥＭ３３、抗ＡＢＣＦ１抗体、ＡＢＣＦ１、抗ＣＦＤＰ１抗体、ＣＦＤＰ１、抗ＰＯＬＲ３ＧＬ抗体、ＰＯＬＲ３ＧＬ、抗ＣＡＤＭ１抗体、ＣＡＤＭ１、抗ＲＮＦ１２８抗体、ＲＮＦ１２８、抗ＡＴＰ６Ｖ１Ｂ１抗体、およびＡＴＰ６Ｖ１Ｂ１からなる群から選択される少なくとも１つを含む、がんの罹患危険度を試験する方法。
（付記７）
前記がんマーカーは、抗ヒト由来ＨＩＲＩＰ３抗体、抗ヒト由来ＦＮＤＣ１１抗体、抗ヒト由来ＳＬＣ１Ａ３抗体、抗ヒト由来ＴＭＥＭ３３抗体、抗ヒト由来ＡＢＣＦ１抗体、抗ヒト由来ＣＦＤＰ１抗体、抗ヒト由来ＰＯＬＲ３ＧＬ抗体、抗ヒト由来ＣＡＤＭ１抗体、抗ヒト由来ＲＮＦ１２８抗体、および抗ヒト由来ＡＴＰ６Ｖ１Ｂ１抗体からなる群から選択される少なくとも１つの抗体を含む、付記６記載の試験方法。
（付記８）
前記がんマーカーは、抗ヒト由来ＨＩＲＩＰ３抗体、抗ヒト由来ＦＮＤＣ１１抗体、抗ヒト由来ＳＬＣ１Ａ３抗体、および抗ヒト由来ＴＭＥＭ３３抗体からなる群から選択される少なくとも１つの抗体を含む、付記６または７記載の試験方法。
（付記９）
前記がんは、乳がん、卵巣がん、膵がん、肝臓がん、胆管がん、大腸がん、結腸がん、直腸がん、胃がん、口腔がん、および肺がんからなる群から選択される少なくとも１つのがんである、付記６から８のいずれかに記載の試験方法。
（付記１０）
前記がんは、乳がんである、付記６から９のいずれかに記載の試験方法。
（付記１１）
前記生体試料は、血液試料である、付記６から１０のいずれかに記載の試験方法。
（付記１２）
がんマーカーの発現測定試薬を含み、
前記がんマーカーは、抗ＨＩＲＩＰ３抗体、ＨＩＲＩＰ３、抗ＦＮＤＣ１１抗体、ＦＮＤＣ１１、抗ＳＬＣ１Ａ３抗体、ＳＬＣ１Ａ３、抗ＴＭＥＭ３３抗体、ＴＭＥＭ３３、抗ＡＢＣＦ１抗体、ＡＢＣＦ１、抗ＣＦＤＰ１抗体、ＣＦＤＰ１、抗ＰＯＬＲ３ＧＬ抗体、ＰＯＬＲ３ＧＬ、抗ＣＡＤＭ１抗体、ＣＡＤＭ１、抗ＲＮＦ１２８抗体、ＲＮＦ１２８、抗ＡＴＰ６Ｖ１Ｂ１抗体、およびＡＴＰ６Ｖ１Ｂ１からなる群から選択される少なくとも１つを含む、がんの試験キット。
（付記１３）
前記がんマーカーは、抗ＨＩＲＩＰ３抗体、抗ＦＮＤＣ１１抗体、抗ＳＬＣ１Ａ３抗体、抗ＴＭＥＭ３３抗体、抗ＡＢＣＦ１抗体、抗ＣＦＤＰ１抗体、抗ＰＯＬＲ３ＧＬ抗体、抗ＣＡＤＭ１抗体、抗ＲＮＦ１２８抗体、および抗ＡＴＰ６Ｖ１Ｂ１抗体からなる群から選択される少なくとも１つの抗体であり、
前記発現測定試薬は、前記がんマーカーに対応する抗原と、前記がんマーカーを検出する検出試薬とを含む、付記１２記載の試験キット。
（付記１４）
前記検出試薬は、標識化されている、付記１３記載の試験キット。
（付記１５）
前記検出試薬は、前記がんマーカーである抗体を認識する抗体である、付記１３または１４記載の試験キット。
（付記１６）
前記がんマーカーに対応する抗原は、担体に固定化されている、付記１３から１５のいずれかに記載の試験キット。
（付記１７）
前記がんマーカーは、ＨＩＲＩＰ３、ＦＮＤＣ１１、ＳＬＣ１Ａ３、ＴＭＥＭ３３、ＡＢＣＦ１、ＣＦＤＰ１、ＰＯＬＲ３ＧＬ、ＣＡＤＭ１、ＲＮＦ１２８、およびＡＴＰ６Ｖ１Ｂ１からなる群から選択される少なくとも１つのがんマーカーのタンパク質であり、
前記発現測定試薬は、前記がんマーカーのタンパク質に結合する物質、および前記がんマーカーのタンパク質と前記結合物質との結合を検出する結合検出試薬を含む、付記１２記載の試験キット。
（付記１８）
前記がんマーカーは、ＨＩＲＩＰ３、ＦＮＤＣ１１、ＳＬＣ１Ａ３、ＴＭＥＭ３３、ＡＢＣＦ１、ＣＦＤＰ１、ＰＯＬＲ３ＧＬ、ＣＡＤＭ１、ＲＮＦ１２８、およびＡＴＰ６Ｖ１Ｂ１からなる群から選択される少なくとも１つのがんマーカーの遺伝子であり、
前記発現測定試薬が、がんマーカーの遺伝子のｍＲＮＡを逆転写により増幅する試薬である、付記１２記載の試験キット。
（付記１９）
前記がんは、乳がん、卵巣がん、膵がん、肝臓がん、胆管がん、大腸がん、結腸がん、直腸がん、胃がん、口腔がん、および肺がんからなる群から選択される少なくとも１つである、付記１２から１８のいずれかに記載の試験キット。
（付記２０）
前記がんは、乳がんである、付記１２から１９のいずれかに記載の試験キット。
（付記２１）
付記６から１１のいずれかに記載の試験方法に使用する、付記１２から２０のいずれかに記載の試験キット。
（付記２２）
被検者の生体試料と、がんマーカーの発現測定試薬とを接触させ、前記生体試料におけるがんマーカーの発現量を測定する工程を含み、
前記がんマーカーは、抗ＨＩＲＩＰ３抗体、ＨＩＲＩＰ３、抗ＦＮＤＣ１１抗体、ＦＮＤＣ１１、抗ＳＬＣ１Ａ３抗体、ＳＬＣ１Ａ３、抗ＴＭＥＭ３３抗体、ＴＭＥＭ３３、抗ＡＢＣＦ１抗体、ＡＢＣＦ１、抗ＣＦＤＰ１抗体、ＣＦＤＰ１、抗ＰＯＬＲ３ＧＬ抗体、ＰＯＬＲ３ＧＬ、抗ＣＡＤＭ１抗体、ＣＡＤＭ１、抗ＲＮＦ１２８抗体、ＲＮＦ１２８、抗ＡＴＰ６Ｖ１Ｂ１抗体、およびＡＴＰ６Ｖ１Ｂ１からなる群から選択される少なくとも１つを含む、がんマーカーの測定方法。
（付記２３）
前記がんマーカーは、抗ＨＩＲＩＰ３抗体、抗ＦＮＤＣ１１抗体、抗ＳＬＣ１Ａ３抗体、抗ＴＭＥＭ３３抗体、抗ＡＢＣＦ１抗体、抗ＣＦＤＰ１抗体、抗ＰＯＬＲ３ＧＬ抗体、抗ＣＡＤＭ１抗体、抗ＲＮＦ１２８抗体、および抗ＡＴＰ６Ｖ１Ｂ１抗体からなる群から選択される少なくとも１つの抗体であり、
前記発現測定試薬は、前記がんマーカーに対応する抗原と、前記がんマーカーを検出する検出試薬とを含み、
前記被検者の生体試料と、前記発現測定試薬とを接触させ、前記生体試料におけるがんマーカーと、前記がんマーカーに対応する抗原と、前記がんマーカーを検出する検出試薬との複合体を形成する工程と、
前記複合体を測定する工程とを含む、付記２２記載の測定方法。
（付記２４）
前記検出試薬は、標識化されている、付記２３記載の測定方法。
（付記２５）
前記検出試薬は、前記がんマーカーである抗体を認識する抗体である、付記２３または２４記載の測定方法。
（付記２６）
前記がんマーカーに対応する抗原は、担体に固定化されている、付記２３から２５のいずれかに記載の測定方法。
（付記２７）
前記がんマーカーは、ＨＩＲＩＰ３、ＦＮＤＣ１１、ＳＬＣ１Ａ３、ＴＭＥＭ３３、ＡＢＣＦ１、ＣＦＤＰ１、ＰＯＬＲ３ＧＬ、ＣＡＤＭ１、ＲＮＦ１２８、およびＡＴＰ６Ｖ１Ｂ１からなる群から選択される少なくとも１つのがんマーカーのタンパク質であり、
前記発現測定試薬は、前記がんマーカーのタンパク質に結合する物質、および前記がんマーカーのタンパク質と前記結合物質との結合を検出する結合検出試薬を含み、
前記被検者の生体試料と、前記発現測定試薬とを接触させ、前記生体試料におけるがんマーカーとの複合体を形成する工程と、
前記複合体を測定する工程とを含む、付記２２記載の測定方法。
（付記２８）
前記がんマーカーは、ＨＩＲＩＰ３、ＦＮＤＣ１１、ＳＬＣ１Ａ３、ＴＭＥＭ３３、ＡＢＣＦ１、ＣＦＤＰ１、ＰＯＬＲ３ＧＬ、ＣＡＤＭ１、ＲＮＦ１２８、およびＡＴＰ６Ｖ１Ｂ１からなる群から選択される少なくとも１つのがんマーカーの遺伝子であり、
前記発現測定試薬が、がんマーカーの遺伝子のｍＲＮＡを逆転写により増幅する試薬であり、
前記被検者の生体試料と、前記発現測定試薬とを接触後、前記がんマーカーの遺伝子を増幅する工程と、
得られた増幅産物を測定する工程とを含む、付記２２記載の測定方法。
（付記２９）
前記がんは、乳がん、卵巣がん、膵がん、肝臓がん、胆管がん、大腸がん、結腸がん、直腸がん、胃がん、口腔がん、および肺がんからなる群から選択される少なくとも１つである、付記２２から２８のいずれかに記載の測定方法。
（付記３０）
前記がんは、乳がんである、付記２２から２９のいずれかに記載の測定方法。
（付記３１）
被検物質から、がんマーカーの発現を抑制する発現抑制物質を、前記治療用候補物質として選択する工程を含み、
前記がんマーカーは、抗ＨＩＲＩＰ３抗体、ＨＩＲＩＰ３、抗ＦＮＤＣ１１抗体、ＦＮＤＣ１１、抗ＳＬＣ１Ａ３抗体、ＳＬＣ１Ａ３、抗ＴＭＥＭ３３抗体、ＴＭＥＭ３３、抗ＡＢＣＦ１抗体、ＡＢＣＦ１、抗ＣＦＤＰ１抗体、ＣＦＤＰ１、抗ＰＯＬＲ３ＧＬ抗体、ＰＯＬＲ３ＧＬ、抗ＣＡＤＭ１抗体、ＣＡＤＭ１、抗ＲＮＦ１２８抗体、ＲＮＦ１２８、抗ＡＴＰ６Ｖ１Ｂ１抗体、およびＡＴＰ６Ｖ１Ｂ１からなる群から選択される少なくとも１つを含む、がん治療薬の候補物質のスクリーニング方法。
（付記３２）
前記がんマーカーは、抗ＨＩＲＩＰ３抗体、抗ＦＮＤＣ１１抗体、抗ＳＬＣ１Ａ３抗体、抗ＴＭＥＭ３３抗体、抗ＡＢＣＦ１抗体、抗ＣＦＤＰ１抗体、抗ＰＯＬＲ３ＧＬ抗体、抗ＣＡＤＭ１抗体、抗ＲＮＦ１２８抗体、および抗ＡＴＰ６Ｖ１Ｂ１抗体からなる群から選択される少なくとも１つの抗体であり、
前記被検物質を生体に投与する工程と、
前記生体において、前記がんマーカーを発現させる工程と、
前記投与後の生体から生体試料を取得する工程と、
前記生体試料におけるがんマーカーの発現を測定する工程と、
前記生体試料におけるがんマーカーの発現量が、前記被検物質を投与していないコントロール由来の生体試料よりも低い前記被検物質を、前記治療用候補物質として選択する工程とを含む、付記３１記載のスクリーニング方法。
（付記３３）
前記がんマーカーは、ＨＩＲＩＰ３、ＦＮＤＣ１１、ＳＬＣ１Ａ３、ＴＭＥＭ３３、ＡＢＣＦ１、ＣＦＤＰ１、ＰＯＬＲ３ＧＬ、ＣＡＤＭ１、ＲＮＦ１２８、およびＡＴＰ６Ｖ１Ｂ１からなる群から選択される少なくとも１つのがんマーカーのタンパク質または遺伝子であり、
前記がんマーカーの発現系に前記被検物質を共存させて、がんマーカーを発現させる工程、前記発現系におけるがんマーカーの発現を検出する工程と、
前記がんマーカーの発現量が、前記被検物質を共存させていないコントロールの発現系よりも低い前記被検物質を、前記治療用候補物質として選択する工程とを含む、付記３１記載のスクリーニング方法。
（付記３４）
前記被検物質が、低分子化合物、ペプチド、タンパク質および核酸からなる群から選択された少なくとも１つである、付記３１から３３のいずれかに記載のスクリーニング方法。 <Appendix>
Some or all of the above embodiments and examples may be described as, but not limited to, the following appendices.
(Appendix 1)
Anti-HIRIP3 antibody, HIRIP3, anti-FNDC11 antibody, FNDC11, anti-SLC1A3 antibody, SLC1A3, anti-TMEM33 antibody, TMEM33, anti-ABCF1 antibody, ABCF1, anti-CFDP1 antibody, CFDP1, anti-POLR3GL antibody, POLR3GL, anti-CADM1 antibody, CAL M1 A cancer marker comprising at least one selected from the group consisting of antibody, RNF128, anti-ATP6V1B1 antibody, and ATP6V1B1.
(Appendix 2)
Anti-human-derived HIRIP3 antibody, anti-human-derived FNDC11 antibody, anti-human-derived SLC1A3 antibody, anti-human-derived TMEM33 antibody, anti-human-derived ABCF1 antibody, anti-human-derived CFDP1 antibody, anti-human-derived POLR3GL antibody, anti-human-derived CADM1 antibody, anti-human The cancer marker according to Appendix 1, which comprises at least one antibody selected from the group consisting of the derived RNF128 antibody and the anti-human derived ATP6V1B1 antibody.
(Appendix 3)
The cancer marker according to Appendix 1 or 2, which comprises at least one antibody selected from the group consisting of anti-human-derived HIRIP3 antibody, anti-human-derived FNDC11 antibody, anti-human-derived SLC1A3 antibody, and anti-human-derived TMEM33 antibody.
(Appendix 4)
The cancer is selected from the group consisting of breast cancer, ovarian cancer, pancreatic cancer, liver cancer, bile duct cancer, colon cancer, colon cancer, rectal cancer, stomach cancer, oral cancer, and lung cancer. The cancer marker according to any one of Appendix 1 to 3, which is at least one cancer.
(Appendix 5)
The cancer marker according to any one of Appendix 1 to 4, wherein the cancer is breast cancer.
(Appendix 6)
Including the step of measuring the expression level of a cancer marker in a biological sample of a subject.
The cancer markers include anti-HIRIP3 antibody, HIRIP3, anti-FNDC11 antibody, FNDC11, anti-SLC1A3 antibody, SLC1A3, anti-TMEM33 antibody, TMEM33, anti-ABCF1 antibody, ABCF1, anti-CFDP1 antibody, CFDP1, anti-POLR3GL antibody, POLR3GL, anti-CAMM1 A method for testing the risk of developing cancer, comprising at least one selected from the group consisting of antibody, CADM1, anti-RNF128 antibody, RNF128, anti-ATP6V1B1 antibody, and ATP6V1B1.
(Appendix 7)
The cancer markers include anti-human-derived HIRIP3 antibody, anti-human-derived FNDC11 antibody, anti-human-derived SLC1A3 antibody, anti-human-derived TMEM33 antibody, anti-human-derived ABCF1 antibody, anti-human-derived CFDP1 antibody, anti-human-derived POLR3GL antibody, and anti-human. The test method according to Appendix 6, which comprises at least one antibody selected from the group consisting of the derived CADM1 antibody, the anti-human derived RNF128 antibody, and the anti-human derived ATP6V1B1 antibody.
(Appendix 8)
The cancer marker according to Appendix 6 or 7, wherein the cancer marker comprises at least one antibody selected from the group consisting of anti-human-derived HIRIP3 antibody, anti-human-derived FNDC11 antibody, anti-human-derived SLC1A3 antibody, and anti-human-derived TMEM33 antibody. Test method.
(Appendix 9)
The cancer is selected from the group consisting of breast cancer, ovarian cancer, pancreatic cancer, liver cancer, bile duct cancer, colon cancer, colon cancer, rectal cancer, stomach cancer, oral cancer, and lung cancer. The test method according to any one of Appendix 6 to 8, which is at least one cancer.
(Appendix 10)
The test method according to any one of Appendix 6 to 9, wherein the cancer is breast cancer.
(Appendix 11)
The test method according to any one of Appendix 6 to 10, wherein the biological sample is a blood sample.
(Appendix 12)
Contains reagents for measuring the expression of cancer markers
The cancer markers include anti-HIRIP3 antibody, HIRIP3, anti-FNDC11 antibody, FNDC11, anti-SLC1A3 antibody, SLC1A3, anti-TMEM33 antibody, TMEM33, anti-ABCF1 antibody, ABCF1, anti-CFDP1 antibody, CFDP1, anti-POLR3GL antibody, POLR3GL, anti-CAMM1 A cancer test kit comprising at least one selected from the group consisting of antibody, CADM1, anti-RNF128 antibody, RNF128, anti-ATP6V1B1 antibody, and ATP6V1B1.
(Appendix 13)
The cancer marker consists of a group consisting of anti-HIRI P3 antibody, anti-FNDC11 antibody, anti-SLC1A3 antibody, anti-TMEM33 antibody, anti-ABCF1 antibody, anti-CFDP1 antibody, anti-POLR3GL antibody, anti-CADM1 antibody, anti-RNF128 antibody, and anti-ATP6V1B1 antibody. At least one antibody of choice,
The test kit according to Appendix 12, wherein the expression measurement reagent includes an antigen corresponding to the cancer marker and a detection reagent for detecting the cancer marker.
(Appendix 14)
The test kit according to Appendix 13, wherein the detection reagent is labeled.
(Appendix 15)
The test kit according to Appendix 13 or 14, wherein the detection reagent is an antibody that recognizes an antibody that is a cancer marker.
(Appendix 16)
The test kit according to any one of Appendix 13 to 15, wherein the antigen corresponding to the cancer marker is immobilized on a carrier.
(Appendix 17)
The cancer marker is a protein of at least one cancer marker selected from the group consisting of HIRIP3, FNDC11, SLC1A3, TMEM33, ABCF1, CFDP1, POLR3GL, CADM1, RNF128, and ATP6V1B1.
The test kit according to Appendix 12, wherein the expression measuring reagent contains a substance that binds to the protein of the cancer marker and a binding detection reagent that detects the binding between the protein of the cancer marker and the binding substance.
(Appendix 18)
The cancer marker is a gene for at least one cancer marker selected from the group consisting of HIRIP3, FNDC11, SLC1A3, TMEM33, ABCF1, CFDP1, POLR3GL, CADM1, RNF128, and ATP6V1B1.
The test kit according to Appendix 12, wherein the expression measurement reagent is a reagent that amplifies the mRNA of a cancer marker gene by reverse transcription.
(Appendix 19)
The cancer is selected from the group consisting of breast cancer, ovarian cancer, pancreatic cancer, liver cancer, bile duct cancer, colon cancer, colon cancer, rectal cancer, stomach cancer, oral cancer, and lung cancer. The test kit according to any one of Appendix 12 to 18, which is at least one.
(Appendix 20)
The test kit according to any one of Appendix 12 to 19, wherein the cancer is breast cancer.
(Appendix 21)
The test kit according to any one of Appendix 12 to 20, which is used for the test method according to any one of Supplementary notes 6 to 11.
(Appendix 22)
It includes a step of contacting a biological sample of a subject with a reagent for measuring the expression of a cancer marker and measuring the expression level of the cancer marker in the biological sample.
The cancer markers include anti-HIRIP3 antibody, HIRIP3, anti-FNDC11 antibody, FNDC11, anti-SLC1A3 antibody, SLC1A3, anti-TMEM33 antibody, TMEM33, anti-ABCF1 antibody, ABCF1, anti-CFDP1 antibody, CFDP1, anti-POLR3GL antibody, POLR3GL, anti-CAMM1 A method for measuring a cancer marker, comprising at least one selected from the group consisting of antibody, CADM1, anti-RNF128 antibody, RNF128, anti-ATP6V1B1 antibody, and ATP6V1B1.
(Appendix 23)
The cancer marker consists of a group consisting of anti-HIRI P3 antibody, anti-FNDC11 antibody, anti-SLC1A3 antibody, anti-TMEM33 antibody, anti-ABCF1 antibody, anti-CFDP1 antibody, anti-POLR3GL antibody, anti-CADM1 antibody, anti-RNF128 antibody, and anti-ATP6V1B1 antibody. At least one antibody of choice,
The expression measuring reagent includes an antigen corresponding to the cancer marker and a detection reagent for detecting the cancer marker.
A complex of a cancer marker in the biological sample, an antigen corresponding to the cancer marker, and a detection reagent for detecting the cancer marker by contacting the biological sample of the subject with the expression measurement reagent. And the process of forming
22. The measuring method according to Appendix 22, which includes a step of measuring the complex.
(Appendix 24)
The measuring method according to Appendix 23, wherein the detection reagent is labeled.
(Appendix 25)
The measuring method according to Appendix 23 or 24, wherein the detection reagent is an antibody that recognizes an antibody that is a cancer marker.
(Appendix 26)
The measuring method according to any one of Appendix 23 to 25, wherein the antigen corresponding to the cancer marker is immobilized on a carrier.
(Appendix 27)
The cancer marker is a protein of at least one cancer marker selected from the group consisting of HIRIP3, FNDC11, SLC1A3, TMEM33, ABCF1, CFDP1, POLR3GL, CADM1, RNF128, and ATP6V1B1.
The expression measuring reagent includes a substance that binds to the protein of the cancer marker and a binding detection reagent that detects the binding between the protein of the cancer marker and the binding substance.
A step of contacting the biological sample of the subject with the expression measuring reagent to form a complex with a cancer marker in the biological sample,
22. The measuring method according to Appendix 22, which includes a step of measuring the complex.
(Appendix 28)
The cancer marker is a gene for at least one cancer marker selected from the group consisting of HIRIP3, FNDC11, SLC1A3, TMEM33, ABCF1, CFDP1, POLR3GL, CADM1, RNF128, and ATP6V1B1.
The expression measurement reagent is a reagent that amplifies the mRNA of a cancer marker gene by reverse transcription.
A step of amplifying the gene of the cancer marker after contacting the biological sample of the subject with the expression measurement reagent, and
22. The measuring method according to Appendix 22, which includes a step of measuring the obtained amplified product.
(Appendix 29)
The cancer is selected from the group consisting of breast cancer, ovarian cancer, pancreatic cancer, liver cancer, bile duct cancer, colon cancer, colon cancer, rectal cancer, stomach cancer, oral cancer, and lung cancer. The measuring method according to any one of Appendix 22 to 28, which is at least one.
(Appendix 30)
The measuring method according to any one of Appendix 22 to 29, wherein the cancer is breast cancer.
(Appendix 31)
A step of selecting an expression-suppressing substance that suppresses the expression of a cancer marker from a test substance as a therapeutic candidate substance is included.
The cancer markers include anti-HIRIP3 antibody, HIRIP3, anti-FNDC11 antibody, FNDC11, anti-SLC1A3 antibody, SLC1A3, anti-TMEM33 antibody, TMEM33, anti-ABCF1 antibody, ABCF1, anti-CFDP1 antibody, CFDP1, anti-POLR3GL antibody, POLR3GL, anti-CAMM1 A method for screening a candidate substance for a cancer therapeutic agent, which comprises at least one selected from the group consisting of antibody, CADM1, anti-RNF128 antibody, RNF128, anti-ATP6V1B1 antibody, and ATP6V1B1.
(Appendix 32)
The cancer marker consists of a group consisting of anti-HIRI P3 antibody, anti-FNDC11 antibody, anti-SLC1A3 antibody, anti-TMEM33 antibody, anti-ABCF1 antibody, anti-CFDP1 antibody, anti-POLR3GL antibody, anti-CADM1 antibody, anti-RNF128 antibody, and anti-ATP6V1B1 antibody. At least one antibody of choice,
The step of administering the test substance to a living body and
The step of expressing the cancer marker in the living body and
The step of obtaining a biological sample from the living body after the administration and
The step of measuring the expression of a cancer marker in the biological sample and
Addendum 31 including a step of selecting the test substance whose expression level of the cancer marker in the biological sample is lower than that of the control-derived biological sample to which the test substance is not administered as the therapeutic candidate substance. The screening method described.
(Appendix 33)
The cancer marker is a protein or gene of at least one cancer marker selected from the group consisting of HIRIP3, FNDC11, SLC1A3, TMEM33, ABCF1, CFDP1, POLR3GL, CADM1, RNF128, and ATP6V1B1.
A step of coexisting the test substance in the expression system of the cancer marker to express the cancer marker, a step of detecting the expression of the cancer marker in the expression system, and a step of detecting the expression of the cancer marker in the expression system.
The screening method according to Appendix 31, which comprises a step of selecting the test substance whose expression level of the cancer marker is lower than that of the control expression system in which the test substance does not coexist as the therapeutic candidate substance. ..
(Appendix 34)
The screening method according to any one of Appendix 31 to 33, wherein the test substance is at least one selected from the group consisting of low molecular weight compounds, peptides, proteins and nucleic acids.
　以上のように、本発明によれば、本発明のマーカーの発現量を測定することによって、被検者のがんの罹患危険度を試験できる。また、本発明のマーカーを用いたスクリーニングにより、がんの治療用候補物質を得ることもできる。このため、本発明は、臨床分野および生化学分野において極めて有用である。 As described above, according to the present invention, the risk of developing cancer in a subject can be tested by measuring the expression level of the marker of the present invention. In addition, a candidate substance for the treatment of cancer can be obtained by screening using the marker of the present invention. Therefore, the present invention is extremely useful in the clinical and biochemical fields.

Claims (34)

  1. 抗ＨＩＲＩＰ３抗体、ＨＩＲＩＰ３、抗ＦＮＤＣ１１抗体、ＦＮＤＣ１１、抗ＳＬＣ１Ａ３抗体、ＳＬＣ１Ａ３、抗ＴＭＥＭ３３抗体、ＴＭＥＭ３３、抗ＡＢＣＦ１抗体、ＡＢＣＦ１、抗ＣＦＤＰ１抗体、ＣＦＤＰ１、抗ＰＯＬＲ３ＧＬ抗体、ＰＯＬＲ３ＧＬ、抗ＣＡＤＭ１抗体、ＣＡＤＭ１、抗ＲＮＦ１２８抗体、ＲＮＦ１２８、抗ＡＴＰ６Ｖ１Ｂ１抗体、およびＡＴＰ６Ｖ１Ｂ１からなる群から選択される少なくとも１つを含む、がんマーカー。 Anti-HIRIP3 antibody, HIRIP3, anti-FNDC11 antibody, FNDC11, anti-SLC1A3 antibody, SLC1A3, anti-TMEM33 antibody, TMEM33, anti-ABCF1 antibody, ABCF1, anti-CFDP1 antibody, CFDP1, anti-POLR3GL antibody, POLR3GL, anti-CADM1 antibody, CAL M1 A cancer marker comprising at least one selected from the group consisting of antibody, RNF128, anti-ATP6V1B1 antibody, and ATP6V1B1.
  2. 抗ヒト由来ＨＩＲＩＰ３抗体、抗ヒト由来ＦＮＤＣ１１抗体、抗ヒト由来ＳＬＣ１Ａ３抗体、抗ヒト由来ＴＭＥＭ３３抗体、抗ヒト由来ＡＢＣＦ１抗体、抗ヒト由来ＣＦＤＰ１抗体、抗ヒト由来ＰＯＬＲ３ＧＬ抗体、抗ヒト由来ＣＡＤＭ１抗体、抗ヒト由来ＲＮＦ１２８抗体、および抗ヒト由来ＡＴＰ６Ｖ１Ｂ１抗体からなる群から選択される少なくとも１つの抗体を含む、請求項１記載のがんマーカー。 Anti-human-derived HIRIP3 antibody, anti-human-derived FNDC11 antibody, anti-human-derived SLC1A3 antibody, anti-human-derived TMEM33 antibody, anti-human-derived ABCF1 antibody, anti-human-derived CFDP1 antibody, anti-human-derived POLR3GL antibody, anti-human-derived CADM1 antibody, anti-human The cancer marker according to claim 1, comprising at least one antibody selected from the group consisting of the derived RNF128 antibody and the anti-human derived ATP6V1B1 antibody.
  3. 抗ヒト由来ＨＩＲＩＰ３抗体、抗ヒト由来ＦＮＤＣ１１抗体、抗ヒト由来ＳＬＣ１Ａ３抗体、および抗ヒト由来ＴＭＥＭ３３抗体からなる群から選択される少なくとも１つの抗体を含む、請求項１または２記載のがんマーカー。 The cancer marker according to claim 1 or 2, which comprises at least one antibody selected from the group consisting of anti-human-derived HIRIP3 antibody, anti-human-derived FNDC11 antibody, anti-human-derived SLC1A3 antibody, and anti-human-derived TMEM33 antibody.
  4. 前記がんは、乳がん、卵巣がん、膵がん、肝臓がん、胆管がん、大腸がん、結腸がん、直腸がん、胃がん、口腔がん、および肺がんからなる群から選択される少なくとも１つのがんである、請求項１から３のいずれか一項に記載のがんマーカー。 The cancer is selected from the group consisting of breast cancer, ovarian cancer, pancreatic cancer, liver cancer, bile duct cancer, colon cancer, colon cancer, rectal cancer, stomach cancer, oral cancer, and lung cancer. The cancer marker according to any one of claims 1 to 3, which is at least one cancer.
  5. 前記がんは、乳がんである、請求項１から４のいずれか一項に記載のがんマーカー。 The cancer marker according to any one of claims 1 to 4, wherein the cancer is breast cancer.
  6. 被検者の生体試料におけるがんマーカーの発現量を測定する工程を含み、
    前記がんマーカーは、抗ＨＩＲＩＰ３抗体、ＨＩＲＩＰ３、抗ＦＮＤＣ１１抗体、ＦＮＤＣ１１、抗ＳＬＣ１Ａ３抗体、ＳＬＣ１Ａ３、抗ＴＭＥＭ３３抗体、ＴＭＥＭ３３、抗ＡＢＣＦ１抗体、ＡＢＣＦ１、抗ＣＦＤＰ１抗体、ＣＦＤＰ１、抗ＰＯＬＲ３ＧＬ抗体、ＰＯＬＲ３ＧＬ、抗ＣＡＤＭ１抗体、ＣＡＤＭ１、抗ＲＮＦ１２８抗体、ＲＮＦ１２８、抗ＡＴＰ６Ｖ１Ｂ１抗体、およびＡＴＰ６Ｖ１Ｂ１からなる群から選択される少なくとも１つを含む、がんの罹患危険度を試験する方法。     Including the step of measuring the expression level of a cancer marker in a biological sample of a subject.
    The cancer markers include anti-HIRIP3 antibody, HIRIP3, anti-FNDC11 antibody, FNDC11, anti-SLC1A3 antibody, SLC1A3, anti-TMEM33 antibody, TMEM33, anti-ABCF1 antibody, ABCF1, anti-CFDP1 antibody, CFDP1, anti-POLR3GL antibody, POLR3GL, anti-CAMM1 A method for testing the risk of developing cancer, comprising at least one selected from the group consisting of antibody, CADM1, anti-RNF128 antibody, RNF128, anti-ATP6V1B1 antibody, and ATP6V1B1.
  7. 前記がんマーカーは、抗ヒト由来ＨＩＲＩＰ３抗体、抗ヒト由来ＦＮＤＣ１１抗体、抗ヒト由来ＳＬＣ１Ａ３抗体、抗ヒト由来ＴＭＥＭ３３抗体、抗ヒト由来ＡＢＣＦ１抗体、抗ヒト由来ＣＦＤＰ１抗体、抗ヒト由来ＰＯＬＲ３ＧＬ抗体、抗ヒト由来ＣＡＤＭ１抗体、抗ヒト由来ＲＮＦ１２８抗体、および抗ヒト由来ＡＴＰ６Ｖ１Ｂ１抗体からなる群から選択される少なくとも１つの抗体を含む、請求項６記載の試験方法。 The cancer markers include anti-human-derived HIRIP3 antibody, anti-human-derived FNDC11 antibody, anti-human-derived SLC1A3 antibody, anti-human-derived TMEM33 antibody, anti-human-derived ABCF1 antibody, anti-human-derived CFDP1 antibody, anti-human-derived POLR3GL antibody, and anti-human. The test method according to claim 6, comprising at least one antibody selected from the group consisting of derived CADM1 antibody, anti-human derived RNF128 antibody, and anti-human derived ATP6V1B1 antibody.
  8. 前記がんマーカーは、抗ヒト由来ＨＩＲＩＰ３抗体、抗ヒト由来ＦＮＤＣ１１抗体、抗ヒト由来ＳＬＣ１Ａ３抗体、および抗ヒト由来ＴＭＥＭ３３抗体からなる群から選択される少なくとも１つの抗体を含む、請求項６または７記載の試験方法。 6. or 7, wherein the cancer marker comprises at least one antibody selected from the group consisting of anti-human-derived HIRIP3 antibody, anti-human-derived FNDC11 antibody, anti-human-derived SLC1A3 antibody, and anti-human-derived TMEM33 antibody. Test method.
  9. 前記がんは、乳がん、卵巣がん、膵がん、肝臓がん、胆管がん、大腸がん、結腸がん、直腸がん、胃がん、口腔がん、および肺がんからなる群から選択される少なくとも１つのがんである、請求項６から８のいずれか一項に記載の試験方法。 The cancer is selected from the group consisting of breast cancer, ovarian cancer, pancreatic cancer, liver cancer, bile duct cancer, colon cancer, colon cancer, rectal cancer, stomach cancer, oral cancer, and lung cancer. The test method according to any one of claims 6 to 8, which is at least one cancer.
  10. 前記がんは、乳がんである、請求項６から９のいずれか一項に記載の試験方法。 The test method according to any one of claims 6 to 9, wherein the cancer is breast cancer.
  11. 前記生体試料は、血液試料である、請求項６から１０のいずれか一項に記載の試験方法。 The test method according to any one of claims 6 to 10, wherein the biological sample is a blood sample.
  12. がんマーカーの発現測定試薬を含み、
    前記がんマーカーは、抗ＨＩＲＩＰ３抗体、ＨＩＲＩＰ３、抗ＦＮＤＣ１１抗体、ＦＮＤＣ１１、抗ＳＬＣ１Ａ３抗体、ＳＬＣ１Ａ３、抗ＴＭＥＭ３３抗体、ＴＭＥＭ３３、抗ＡＢＣＦ１抗体、ＡＢＣＦ１、抗ＣＦＤＰ１抗体、ＣＦＤＰ１、抗ＰＯＬＲ３ＧＬ抗体、ＰＯＬＲ３ＧＬ、抗ＣＡＤＭ１抗体、ＣＡＤＭ１、抗ＲＮＦ１２８抗体、ＲＮＦ１２８、抗ＡＴＰ６Ｖ１Ｂ１抗体、およびＡＴＰ６Ｖ１Ｂ１からなる群から選択される少なくとも１つを含む、がんの試験キット。     Contains reagents for measuring the expression of cancer markers
    The cancer markers include anti-HIRIP3 antibody, HIRIP3, anti-FNDC11 antibody, FNDC11, anti-SLC1A3 antibody, SLC1A3, anti-TMEM33 antibody, TMEM33, anti-ABCF1 antibody, ABCF1, anti-CFDP1 antibody, CFDP1, anti-POLR3GL antibody, POLR3GL, anti-CAMM1 A cancer test kit comprising at least one selected from the group consisting of antibody, CADM1, anti-RNF128 antibody, RNF128, anti-ATP6V1B1 antibody, and ATP6V1B1.
  13. 前記がんマーカーは、抗ＨＩＲＩＰ３抗体、抗ＦＮＤＣ１１抗体、抗ＳＬＣ１Ａ３抗体、抗ＴＭＥＭ３３抗体、抗ＡＢＣＦ１抗体、抗ＣＦＤＰ１抗体、抗ＰＯＬＲ３ＧＬ抗体、抗ＣＡＤＭ１抗体、抗ＲＮＦ１２８抗体、および抗ＡＴＰ６Ｖ１Ｂ１抗体からなる群から選択される少なくとも１つの抗体であり、
    前記発現測定試薬は、前記がんマーカーに対応する抗原と、前記がんマーカーを検出する検出試薬とを含む、請求項１２記載の試験キット。     The cancer marker consists of a group consisting of anti-HIRI P3 antibody, anti-FNDC11 antibody, anti-SLC1A3 antibody, anti-TMEM33 antibody, anti-ABCF1 antibody, anti-CFDP1 antibody, anti-POLR3GL antibody, anti-CADM1 antibody, anti-RNF128 antibody, and anti-ATP6V1B1 antibody. At least one antibody of choice,
    The test kit according to claim 12, wherein the expression measurement reagent includes an antigen corresponding to the cancer marker and a detection reagent for detecting the cancer marker.
  14. 前記検出試薬は、標識化されている、請求項１３記載の試験キット。 13. The test kit according to claim 13, wherein the detection reagent is labeled.
  15. 前記検出試薬は、前記がんマーカーである抗体を認識する抗体である、請求項１３または１４記載の試験キット。 The test kit according to claim 13 or 14, wherein the detection reagent is an antibody that recognizes an antibody that is a cancer marker.
  16. 前記がんマーカーに対応する抗原は、担体に固定化されている、請求項１３から１５のいずれか一項に記載の試験キット。 The test kit according to any one of claims 13 to 15, wherein the antigen corresponding to the cancer marker is immobilized on a carrier.
  17. 前記がんマーカーは、ＨＩＲＩＰ３、ＦＮＤＣ１１、ＳＬＣ１Ａ３、ＴＭＥＭ３３、ＡＢＣＦ１、ＣＦＤＰ１、ＰＯＬＲ３ＧＬ、ＣＡＤＭ１、ＲＮＦ１２８、およびＡＴＰ６Ｖ１Ｂ１からなる群から選択される少なくとも１つのがんマーカーのタンパク質であり、
    前記発現測定試薬は、前記がんマーカーのタンパク質に結合する物質、および前記がんマーカーのタンパク質と前記結合物質との結合を検出する結合検出試薬を含む、請求項１２記載の試験キット。     The cancer marker is a protein of at least one cancer marker selected from the group consisting of HIRIP3, FNDC11, SLC1A3, TMEM33, ABCF1, CFDP1, POLR3GL, CADM1, RNF128, and ATP6V1B1.
    The test kit according to claim 12, wherein the expression measuring reagent includes a substance that binds to the protein of the cancer marker and a binding detection reagent that detects the binding between the protein of the cancer marker and the binding substance.
  18. 前記がんマーカーは、ＨＩＲＩＰ３、ＦＮＤＣ１１、ＳＬＣ１Ａ３、ＴＭＥＭ３３、ＡＢＣＦ１、ＣＦＤＰ１、ＰＯＬＲ３ＧＬ、ＣＡＤＭ１、ＲＮＦ１２８、およびＡＴＰ６Ｖ１Ｂ１からなる群から選択される少なくとも１つのがんマーカーの遺伝子であり、
    前記発現測定試薬が、がんマーカーの遺伝子のｍＲＮＡを逆転写により増幅する試薬である、請求項１２記載の試験キット。     The cancer marker is a gene for at least one cancer marker selected from the group consisting of HIRIP3, FNDC11, SLC1A3, TMEM33, ABCF1, CFDP1, POLR3GL, CADM1, RNF128, and ATP6V1B1.
    The test kit according to claim 12, wherein the expression measurement reagent is a reagent that amplifies mRNA of a gene of a cancer marker by reverse transcription.
  19. 前記がんは、乳がん、卵巣がん、膵がん、肝臓がん、胆管がん、大腸がん、結腸がん、直腸がん、胃がん、口腔がん、および肺がんからなる群から選択される少なくとも１つである、請求項１２から１８のいずれか一項に記載の試験キット。 The cancer is selected from the group consisting of breast cancer, ovarian cancer, pancreatic cancer, liver cancer, bile duct cancer, colon cancer, colon cancer, rectal cancer, stomach cancer, oral cancer, and lung cancer. The test kit according to any one of claims 12 to 18, which is at least one.
  20. 前記がんは、乳がんである、請求項１２から１９のいずれか一項に記載の試験キット。 The test kit according to any one of claims 12 to 19, wherein the cancer is breast cancer.
  21. 請求項６から１１のいずれか一項に記載の試験方法に使用する、請求項１２から２０のいずれか一項に記載の試験キット。 The test kit according to any one of claims 12 to 20, which is used for the test method according to any one of claims 6 to 11.
  22. 被検者の生体試料と、がんマーカーの発現測定試薬とを接触させ、前記生体試料におけるがんマーカーの発現量を測定する工程を含み、
    前記がんマーカーは、抗ＨＩＲＩＰ３抗体、ＨＩＲＩＰ３、抗ＦＮＤＣ１１抗体、ＦＮＤＣ１１、抗ＳＬＣ１Ａ３抗体、ＳＬＣ１Ａ３、抗ＴＭＥＭ３３抗体、ＴＭＥＭ３３、抗ＡＢＣＦ１抗体、ＡＢＣＦ１、抗ＣＦＤＰ１抗体、ＣＦＤＰ１、抗ＰＯＬＲ３ＧＬ抗体、ＰＯＬＲ３ＧＬ、抗ＣＡＤＭ１抗体、ＣＡＤＭ１、抗ＲＮＦ１２８抗体、ＲＮＦ１２８、抗ＡＴＰ６Ｖ１Ｂ１抗体、およびＡＴＰ６Ｖ１Ｂ１からなる群から選択される少なくとも１つを含む、がんマーカーの測定方法。     It includes a step of contacting a biological sample of a subject with a reagent for measuring the expression of a cancer marker and measuring the expression level of the cancer marker in the biological sample.
    The cancer markers include anti-HIRIP3 antibody, HIRIP3, anti-FNDC11 antibody, FNDC11, anti-SLC1A3 antibody, SLC1A3, anti-TMEM33 antibody, TMEM33, anti-ABCF1 antibody, ABCF1, anti-CFDP1 antibody, CFDP1, anti-POLR3GL antibody, POLR3GL, anti-CAMM1 A method for measuring a cancer marker, comprising at least one selected from the group consisting of antibody, CADM1, anti-RNF128 antibody, RNF128, anti-ATP6V1B1 antibody, and ATP6V1B1.
  23. 前記がんマーカーは、抗ＨＩＲＩＰ３抗体、抗ＦＮＤＣ１１抗体、抗ＳＬＣ１Ａ３抗体、抗ＴＭＥＭ３３抗体、抗ＡＢＣＦ１抗体、抗ＣＦＤＰ１抗体、抗ＰＯＬＲ３ＧＬ抗体、抗ＣＡＤＭ１抗体、抗ＲＮＦ１２８抗体、および抗ＡＴＰ６Ｖ１Ｂ１抗体からなる群から選択される少なくとも１つの抗体であり、
    前記発現測定試薬は、前記がんマーカーに対応する抗原と、前記がんマーカーを検出する検出試薬とを含み、
    前記被検者の生体試料と、前記発現測定試薬とを接触させ、前記生体試料におけるがんマーカーと、前記がんマーカーに対応する抗原と、前記がんマーカーを検出する検出試薬との複合体を形成する工程と、
    前記複合体を測定する工程とを含む、請求項２２記載の測定方法。     The cancer marker consists of a group consisting of anti-HIRI P3 antibody, anti-FNDC11 antibody, anti-SLC1A3 antibody, anti-TMEM33 antibody, anti-ABCF1 antibody, anti-CFDP1 antibody, anti-POLR3GL antibody, anti-CADM1 antibody, anti-RNF128 antibody, and anti-ATP6V1B1 antibody. At least one antibody of choice,
    The expression measuring reagent includes an antigen corresponding to the cancer marker and a detection reagent for detecting the cancer marker.
    A complex of a cancer marker in the biological sample, an antigen corresponding to the cancer marker, and a detection reagent for detecting the cancer marker by contacting the biological sample of the subject with the expression measurement reagent. And the process of forming
    The measuring method according to claim 22, further comprising the step of measuring the complex.
  24. 前記検出試薬は、標識化されている、請求項２３記載の測定方法。 23. The measuring method according to claim 23, wherein the detection reagent is labeled.
  25. 前記検出試薬は、前記がんマーカーである抗体を認識する抗体である、請求項２３または２４記載の測定方法。 The measuring method according to claim 23 or 24, wherein the detection reagent is an antibody that recognizes an antibody that is a cancer marker.
  26. 前記がんマーカーに対応する抗原は、担体に固定化されている、請求項２３から２５のいずれか一項に記載の測定方法。 The measuring method according to any one of claims 23 to 25, wherein the antigen corresponding to the cancer marker is immobilized on a carrier.
  27. 前記がんマーカーは、ＨＩＲＩＰ３、ＦＮＤＣ１１、ＳＬＣ１Ａ３、ＴＭＥＭ３３、ＡＢＣＦ１、ＣＦＤＰ１、ＰＯＬＲ３ＧＬ、ＣＡＤＭ１、ＲＮＦ１２８、およびＡＴＰ６Ｖ１Ｂ１からなる群から選択される少なくとも１つのがんマーカーのタンパク質であり、
    前記発現測定試薬は、前記がんマーカーのタンパク質に結合する物質、および前記がんマーカーのタンパク質と前記結合物質との結合を検出する結合検出試薬を含み、
    前記被検者の生体試料と、前記発現測定試薬とを接触させ、前記生体試料におけるがんマーカーと、前記がんマーカーのタンパク質に結合する物質との複合体を形成する工程と、
    前記複合体を測定する工程とを含む、請求項２２記載の測定方法。     The cancer marker is a protein of at least one cancer marker selected from the group consisting of HIRIP3, FNDC11, SLC1A3, TMEM33, ABCF1, CFDP1, POLR3GL, CADM1, RNF128, and ATP6V1B1.
    The expression measuring reagent includes a substance that binds to the protein of the cancer marker and a binding detection reagent that detects the binding between the protein of the cancer marker and the binding substance.
    A step of contacting the biological sample of the subject with the expression measurement reagent to form a complex of the cancer marker in the biological sample and a substance that binds to the protein of the cancer marker.
    The measuring method according to claim 22, further comprising the step of measuring the complex.
  28. 前記がんマーカーは、ＨＩＲＩＰ３、ＦＮＤＣ１１、ＳＬＣ１Ａ３、ＴＭＥＭ３３、ＡＢＣＦ１、ＣＦＤＰ１、ＰＯＬＲ３ＧＬ、ＣＡＤＭ１、ＲＮＦ１２８、およびＡＴＰ６Ｖ１Ｂ１からなる群から選択される少なくとも１つのがんマーカーの遺伝子であり、
    前記発現測定試薬が、がんマーカーの遺伝子のｍＲＮＡを逆転写により増幅する試薬であり、
    前記被検者の生体試料と、前記発現測定試薬とを接触後、前記がんマーカーの遺伝子を増幅する工程と、
    得られた増幅産物を測定する工程とを含む、請求項２２記載の測定方法。     The cancer marker is a gene for at least one cancer marker selected from the group consisting of HIRIP3, FNDC11, SLC1A3, TMEM33, ABCF1, CFDP1, POLR3GL, CADM1, RNF128, and ATP6V1B1.
    The expression measurement reagent is a reagent that amplifies the mRNA of a cancer marker gene by reverse transcription.
    A step of amplifying the gene of the cancer marker after contacting the biological sample of the subject with the expression measurement reagent, and
    The measuring method according to claim 22, further comprising a step of measuring the obtained amplification product.
  29. 前記がんは、乳がん、卵巣がん、膵がん、肝臓がん、胆管がん、大腸がん、結腸がん、直腸がん、胃がん、口腔がん、および肺がんからなる群から選択される少なくとも１つである、請求項２２から２８のいずれか一項に記載の測定方法。 The cancer is selected from the group consisting of breast cancer, ovarian cancer, pancreatic cancer, liver cancer, bile duct cancer, colon cancer, colon cancer, rectal cancer, stomach cancer, oral cancer, and lung cancer. The measuring method according to any one of claims 22 to 28, which is at least one.
  30. 前記がんは、乳がんである、請求項２２から２９のいずれか一項に記載の測定方法。 The measuring method according to any one of claims 22 to 29, wherein the cancer is breast cancer.
  31. 被検物質から、がんマーカーの発現を抑制する発現抑制物質を、前記治療用候補物質として選択する工程を含み、
    前記がんマーカーは、抗ＨＩＲＩＰ３抗体、ＨＩＲＩＰ３、抗ＦＮＤＣ１１抗体、ＦＮＤＣ１１、抗ＳＬＣ１Ａ３抗体、ＳＬＣ１Ａ３、抗ＴＭＥＭ３３抗体、ＴＭＥＭ３３、抗ＡＢＣＦ１抗体、ＡＢＣＦ１、抗ＣＦＤＰ１抗体、ＣＦＤＰ１、抗ＰＯＬＲ３ＧＬ抗体、ＰＯＬＲ３ＧＬ、抗ＣＡＤＭ１抗体、ＣＡＤＭ１、抗ＲＮＦ１２８抗体、ＲＮＦ１２８、抗ＡＴＰ６Ｖ１Ｂ１抗体、およびＡＴＰ６Ｖ１Ｂ１からなる群から選択される少なくとも１つを含む、がん治療薬の候補物質のスクリーニング方法。     A step of selecting an expression-suppressing substance that suppresses the expression of a cancer marker from a test substance as a therapeutic candidate substance is included.
    The cancer markers include anti-HIRIP3 antibody, HIRIP3, anti-FNDC11 antibody, FNDC11, anti-SLC1A3 antibody, SLC1A3, anti-TMEM33 antibody, TMEM33, anti-ABCF1 antibody, ABCF1, anti-CFDP1 antibody, CFDP1, anti-POLR3GL antibody, POLR3GL, anti-CAMM1 A method for screening a candidate substance for a cancer therapeutic agent, which comprises at least one selected from the group consisting of antibody, CADM1, anti-RNF128 antibody, RNF128, anti-ATP6V1B1 antibody, and ATP6V1B1.
  32. 前記がんマーカーは、抗ＨＩＲＩＰ３抗体、抗ＦＮＤＣ１１抗体、抗ＳＬＣ１Ａ３抗体、抗ＴＭＥＭ３３抗体、抗ＡＢＣＦ１抗体、抗ＣＦＤＰ１抗体、抗ＰＯＬＲ３ＧＬ抗体、抗ＣＡＤＭ１抗体、抗ＲＮＦ１２８抗体、および抗ＡＴＰ６Ｖ１Ｂ１抗体からなる群から選択される少なくとも１つの抗体であり、
    前記被検物質を生体に投与する工程と、
    前記生体において、前記がんマーカーを発現させる工程と、
    前記投与後の生体から生体試料を取得する工程と、
    前記生体試料におけるがんマーカーの発現を測定する工程と、
    前記生体試料におけるがんマーカーの発現量が、前記被検物質を投与していないコントロール由来の生体試料よりも低い前記被検物質を、前記治療用候補物質として選択する工程とを含む、請求項３１記載のスクリーニング方法。     The cancer marker consists of a group consisting of anti-HIRI P3 antibody, anti-FNDC11 antibody, anti-SLC1A3 antibody, anti-TMEM33 antibody, anti-ABCF1 antibody, anti-CFDP1 antibody, anti-POLR3GL antibody, anti-CADM1 antibody, anti-RNF128 antibody, and anti-ATP6V1B1 antibody. At least one antibody of choice,
    The step of administering the test substance to a living body and
    The step of expressing the cancer marker in the living body and
    The step of obtaining a biological sample from the living body after the administration and
    The step of measuring the expression of a cancer marker in the biological sample and
    The claim includes a step of selecting the test substance whose expression level of the cancer marker in the biological sample is lower than that of the control-derived biological sample to which the test substance has not been administered as the therapeutic candidate substance. 31. The screening method.
  33. 前記がんマーカーは、ＨＩＲＩＰ３、ＦＮＤＣ１１、ＳＬＣ１Ａ３、ＴＭＥＭ３３、ＡＢＣＦ１、ＣＦＤＰ１、ＰＯＬＲ３ＧＬ、ＣＡＤＭ１、ＲＮＦ１２８、およびＡＴＰ６Ｖ１Ｂ１からなる群から選択される少なくとも１つのがんマーカーのタンパク質または遺伝子であり、
    前記がんマーカーの発現系に前記被検物質を共存させて、がんマーカーを発現させる工程、前記発現系におけるがんマーカーの発現を検出する工程と、
    前記がんマーカーの発現量が、前記被検物質を共存させていないコントロールの発現系よりも低い前記被検物質を、前記治療用候補物質として選択する工程とを含む、請求項３１記載のスクリーニング方法。     The cancer marker is a protein or gene of at least one cancer marker selected from the group consisting of HIRIP3, FNDC11, SLC1A3, TMEM33, ABCF1, CFDP1, POLR3GL, CADM1, RNF128, and ATP6V1B1.
    A step of coexisting the test substance in the expression system of the cancer marker to express the cancer marker, a step of detecting the expression of the cancer marker in the expression system, and a step of detecting the expression of the cancer marker in the expression system.
    The screening according to claim 31, which comprises a step of selecting the test substance whose expression level of the cancer marker is lower than that of the control expression system in which the test substance does not coexist as the therapeutic candidate substance. Method.
  34. 前記被検物質が、低分子化合物、ペプチド、タンパク質および核酸からなる群から選択された少なくとも１つである、請求項３１から３３のいずれか一項に記載のスクリーニング方法。 The screening method according to any one of claims 31 to 33, wherein the test substance is at least one selected from the group consisting of low molecular weight compounds, peptides, proteins and nucleic acids.
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