JP7445334B1 - 膵臓癌に特異的な遺伝子発現パターンの検出及びca19-9の測定の併用による膵臓癌の検出 - Google Patents
膵臓癌に特異的な遺伝子発現パターンの検出及びca19-9の測定の併用による膵臓癌の検出 Download PDFInfo
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Abstract
Description
[1] 被験体における以下の56個の遺伝子セットA56個の遺伝子の発現レベルとCA19-9値の測定値に基づいて膵臓癌の検出を補助する方法:
遺伝子セットA
(1)Abhydrolase domain containing 3 (ABHD3)
(2)Abl-interactor 1 (ABI1)
(3)Acyl-CoA synthetase long-chain family member 3 (ACSL3)
(4)Aldo-keto reductase family 1, member B1 (aldose reductase) (AKR1B1)
(5)ATPase, Class VI, type 11B (ATP11B)
(6)UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 5 (B3GNT5)
(7)BTB and CNC homology 1, basic leucine zipper transcription factor 1 (BACH1)
(8)Chromosome 11 open reading frame 2 (C11orf2)
(9)Chromosome 2 open reading frame 81 (C2orf81)
(10)Cyclin Y-like 1 (CCNYL1)
(11)Centromere protein N (CENPN)
(12)Complement factor H-related 3 (CFHR3)
(13)C-type lectin domain family 4, member D (CLEC4D)
(14)Collagen, type XVII, alpha 1 (COL17A1)
(15)Cytochrome b5 reductase 4 (CYB5R4)
(16)DENN/MADD domain containing 1B (DENND1B)
(17)Enoyl CoA hydratase domain containing 3 (ECHDC3)
(18)Ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1)
(19)Family with sequence similarity 198, member B (FAM198B)
(20)Family with sequence similarity 49, member B (FAM49B)
(21)Fatty acyl CoA reductase 1 (FAR1)
(22)Fibrinogen-like 2 (FGL2)
(23)Fibronectin type III domain containing 3B (FNDC3B)
(24)Fucose-1-phosphate guanylyltransferase (FPGT)
(25)UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 4 (GalNAc-T4) (GALNT4)
(26)HEAT repeat containing 5A (HEATR5A)
(27)HIV-1 Tat interactive protein 2, 30kDa (HTATIP2)
(28)Interferon gamma receptor 1 (IFNGR1)
(29)IKBKB interacting protein (IKBIP)
(30)Lactate dehydrogenase A (LDHA)
(31)Lysophosphatidic acid receptor 6 (LPAR6)
(32)Membrane-bound transcription factor peptidase, site 2 (MBTPS2)
(33)Minichromosome maintenance complex binding protein (MCMBP)
(34)Mesoderm induction early response 1 homolog (Xenopus laevis) (MIER1)
(35)Nuclear factor (erythroid-derived 2)-like 2 (NFE2L2)
(36)Oligonucleotide/oligosaccharide-binding fold containing 2A (OBFC2A)
(37)Oxysterol binding protein-like 8 (OSBPL8)
(38)Peptidylprolyl isomerase H (cyclophilin H) (PPIH)
(39)Protein phosphatase 1, regulatory (inhibitor) subunit 13 like (PPP1R13L)
(40)PR domain containing 5 (PRDM5)
(41)Protein tyrosine phosphatase, receptor type, C (PTPRC)
(42)RAB10, member RAS oncogene family (RAB10)
(43)Ribosomal protein, large, P1 (RPLP1)
(44)Ras-related GTP binding D (RRAGD)
(45)Solute carrier family 22, member 15 (SLC22A15)
(46)Solute carrier family 44, member 1 (SLC44A1)
(47)Schlafen family member 12 (SLFN12)
(48)S1 RNA binding domain 1 (SRBD1)
(49)Tet oncogene family member 2 (TET2)
(50)Transducin-like enhancer of split 2 (E(sp1) homolog, Drosophila) (TLE2)
(51)Ubiquitin-conjugating enzyme E2W (putative) (UBE2W)
(52)Ubiquitination factor E4A (UBE4A)
(53)Ubiquitin specific peptidase 15 (USP15)
(54)WD repeat and SOCS box containing 1 (WSB1)
(55)Zinc finger E-box binding homeobox 2 (ZEB2)
(56)Zinc metallopeptidase (STE24 homolog, S. cerevisiae) (ZMPSTE24)
[2] 被験体の遺伝子の発現レベルを、被験体の末梢血細胞のmRNAを用いて測定する、[1]の方法。
[3] 遺伝子の発現レベルを、請求項1に記載の56個の遺伝子セットAの56個の遺伝子の塩基配列からなるヌクレオチド又はその一部配列を含むヌクレオチドをターゲットとした定量PCRにより測定し、CA19-9の測定値と併用する、[1]の方法。
[4] 以下の工程を含む、[1]~[3]のいずれかの方法:
(1)被験体より採取した末梢血細胞よりmRNAを抽出する工程;
(2)遺伝子セットAの56個の遺伝子をPCRにより増幅し、Ct(Cycle threshold)値を得て、GAPDH等のハウスキーピング遺伝子のCt値により標準化し、標準化Ct値を得る工程;
(3)被験体より採取した生体試料中のCA19-9を測定する工程;
(4)遺伝子セットAの各遺伝子の標準化Ct値およびCA19-9測定値より、膵臓癌が陽性であるか、陰性であるかの判断を補助するための値を算出する工程。
[5] 以下の工程を含む[4]の方法であって、最終判定値Zが0より大きい場合に膵臓癌が陽性であると判定する方法:
(1) [4](2)の工程で得られた標準化Ct値より以下の判別式Iを用いてP値を算出する工程
判別式I: intercept + Σ (beta i × X i)
[式において、interceptは定数、beta iは遺伝子セットAの56個の遺伝子のi番目の遺伝子に対する係数、x iは遺伝子セットAの56個の遺伝子それぞれの遺伝子のbeta × Xを合計することを示す。];及び
(2) [4](3)の工程で得られたCA19-9の測定値をC値とし、P値とC値を以下の判別式IIに代入し、最終判定値Zを得る工程
判別式II:-2.9448 + (0.0090864 x P) + (0.9329593 x Loge C)。
[6] 56個の遺伝子セットAを用いる判別式におけるintercept及び各遺伝子のbeta iが以下に示す値である、[5]の膵臓癌を検出する方法:
intercept: -298.018
遺伝子セットA
(1)Abhydrolase domain containing 3 (ABHD3)
(2)Abl-interactor 1 (ABI1)
(3)Acyl-CoA synthetase long-chain family member 3 (ACSL3)
(4)Aldo-keto reductase family 1, member B1 (aldose reductase) (AKR1B1)
(5)ATPase, Class VI, type 11B (ATP11B)
(6)UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 5 (B3GNT5)
(7)BTB and CNC homology 1, basic leucine zipper transcription factor 1 (BACH1)
(8)Chromosome 11 open reading frame 2 (C11orf2)
(9)Chromosome 2 open reading frame 81 (C2orf81)
(10)Cyclin Y-like 1 (CCNYL1)
(11)Centromere protein N (CENPN)
(12)Complement factor H-related 3 (CFHR3)
(13)C-type lectin domain family 4, member D (CLEC4D)
(14)Collagen, type XVII, alpha 1 (COL17A1)
(15)Cytochrome b5 reductase 4 (CYB5R4)
(16)DENN/MADD domain containing 1B (DENND1B)
(17)Enoyl CoA hydratase domain containing 3 (ECHDC3)
(18)Ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1)
(19)Family with sequence similarity 198, member B (FAM198B)
(20)Family with sequence similarity 49, member B (FAM49B)
(21)Fatty acyl CoA reductase 1 (FAR1)
(22)Fibrinogen-like 2 (FGL2)
(23)Fibronectin type III domain containing 3B (FNDC3B)
(24)Fucose-1-phosphate guanylyltransferase (FPGT)
(25)UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 4 (GalNAc-T4) (GALNT4)
(26)HEAT repeat containing 5A (HEATR5A)
(27)HIV-1 Tat interactive protein 2, 30kDa (HTATIP2)
(28)Interferon gamma receptor 1 (IFNGR1)
(29)IKBKB interacting protein (IKBIP)
(30)Lactate dehydrogenase A (LDHA)
(31)Lysophosphatidic acid receptor 6 (LPAR6)
(32)Membrane-bound transcription factor peptidase, site 2 (MBTPS2)
(33)Minichromosome maintenance complex binding protein (MCMBP)
(34)Mesoderm induction early response 1 homolog (Xenopus laevis) (MIER1)
(35)Nuclear factor (erythroid-derived 2)-like 2 (NFE2L2)
(36)Oligonucleotide/oligosaccharide-binding fold containing 2A (OBFC2A)
(37)Oxysterol binding protein-like 8 (OSBPL8)
(38)Peptidylprolyl isomerase H (cyclophilin H) (PPIH)
(39)Protein phosphatase 1, regulatory (inhibitor) subunit 13 like (PPP1R13L)
(40)PR domain containing 5 (PRDM5)
(41)Protein tyrosine phosphatase, receptor type, C (PTPRC)
(42)RAB10, member RAS oncogene family (RAB10)
(43)Ribosomal protein, large, P1 (RPLP1)
(44)Ras-related GTP binding D (RRAGD)
(45)Solute carrier family 22, member 15 (SLC22A15)
(46)Solute carrier family 44, member 1 (SLC44A1)
(47)Schlafen family member 12 (SLFN12)
(48)S1 RNA binding domain 1 (SRBD1)
(49)Tet oncogene family member 2 (TET2)
(50)Transducin-like enhancer of split 2 (E(sp1) homolog, Drosophila) (TLE2)
(51)Ubiquitin-conjugating enzyme E2W (putative) (UBE2W)
(52)Ubiquitination factor E4A (UBE4A)
(53)Ubiquitin specific peptidase 15 (USP15)
(54)WD repeat and SOCS box containing 1 (WSB1)
(55)Zinc finger E-box binding homeobox 2 (ZEB2)
(56)Zinc metallopeptidase (STE24 homolog, S. cerevisiae) (ZMPSTE24)
[8] 一部配列を含むヌクレオチドがPCR用プライマーである、[7]の試薬。
1.遺伝子発現解析及びCA19-9の測定の併用による膵臓癌の検出
(i)遺伝子発現解析
本発明の方法で用いる遺伝子は、膵臓癌で発現レベルが変動する56個の遺伝子である。これらの56個の遺伝子の発現レベルを測定し発現プロファイルを解析すればよい。
(1)Abhydrolase domain containing 3 (ABHD3)(NM_138340.4)(配列番号1)
(2)Abl-interactor 1 (ABI1)(NM_005470.3)(配列番号2)
(3)Acyl-CoA synthetase long-chain family member 3 (ACSL3)(NM_004457.3)(配列番号3)
(4)Aldo-keto reductase family 1, member B1 (aldose reductase) (AKR1B1)(NM_001628.2)(配列番号4)
(5)ATPase, Class VI, type 11B (ATP11B)(NM_014616.2)(配列番号5)
(6)UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 5 (B3GNT5)(NM_032047.4)(配列番号6)
(7)BTB and CNC homology 1, basic leucine zipper transcription factor 1 (BACH1)(NM_001186.3)(配列番号7)
(8)Chromosome 11 open reading frame 2 (C11orf2)(NM_013265.3)(配列番号8)(vacuolar protein sorting 51 homolog (S. cerevisiae) (VPS51)とも呼ぶ)
(9)Chromosome 2 open reading frame 81 (C2orf81)(NM_001145054.1)(配列番号9)
(10)Cyclin Y-like 1 (CCNYL1)(NM_152523.2)(配列番号10)
(11)Centromere protein N (CENPN)(NM_018455.5)(配列番号11)
(12)Complement factor H-related 3 (CFHR3)(NM_021023.5)(配列番号12)
(13)C-type lectin domain family 4, member D (CLEC4D)(NM_080387.4)(配列番号13)
(14)Collagen, type XVII, alpha 1 (COL17A1)(NM_000494.3)(配列番号14)
(15)Cytochrome b5 reductase 4 (CYB5R4)(NM_016230.3)(配列番号15)
(16)DENN/MADD domain containing 1B (DENND1B)(NM_001195215.1)(配列番号16)
(17)Enoyl CoA hydratase domain containing 3 (ECHDC3)(NM_024693.4)(配列番号17)
(18)Ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1)(NM_001776.5)(配列番号18)
(19)Family with sequence similarity 198, member B (FAM198B)(NM_016613.6)(配列番号19)
(20)Family with sequence similarity 49, member B (FAM49B)(NM_016623.4)(配列番号20)
(21)Fatty acyl CoA reductase 1 (FAR1)(NM_032228.5)(配列番号21)
(22)Fibrinogen-like 2 (FGL2)(NM_006682.2)(配列番号22)
(23)Fibronectin type III domain containing 3B (FNDC3B)(NM_022763.3)(配列番号23)
(24)Fucose-1-phosphate guanylyltransferase (FPGT)(NM_003838.4)(配列番号24)
(25)UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 4 (GalNAc-T4) (GALNT4)(NM_003774.4)(配列番号25)
(26)HEAT repeat containing 5A (HEATR5A)(NM_015473.3)(配列番号26)
(27)HIV-1 Tat interactive protein 2, 30kDa (HTATIP2)(NM_006410.4)(配列番号27)
(28)Interferon gamma receptor 1 (IFNGR1)(NM_000416.2)(配列番号28)
(29)IKBKB interacting protein (IKBIP)(NM_201612.2)(配列番号29)
(30)Lactate dehydrogenase A (LDHA)(NM_005566.3)(配列番号30)
(31)Lysophosphatidic acid receptor 6 (LPAR6)(NM_005767.5)(配列番号31)
(32)Membrane-bound transcription factor peptidase, site 2 (MBTPS2)(NM_015884.3)(配列番号32)
(33)Minichromosome maintenance complex binding protein (MCMBP)(NM_024834.3)(配列番号33)
(34)Mesoderm induction early response 1 homolog (Xenopus laevis) (MIER1)(NM_020948.3)(配列番号34)
(35)Nuclear factor (erythroid-derived 2)-like 2 (NFE2L2)(NM_006164.4)(配列番号35)
(36)Oligonucleotide/oligosaccharide-binding fold containing 2A (OBFC2A)(NM_001031716.2)(配列番号36)(nucleic acid binding protein 1 (NABP1)とも呼ぶ)
(37)Oxysterol binding protein-like 8 (OSBPL8)(NM_020841.4)(配列番号37)
(38)Peptidylprolyl isomerase H (cyclophilin H) (PPIH)(NM_006347.3)(配列番号38)
(39)Protein phosphatase 1, regulatory (inhibitor) subunit 13 like (PPP1R13L)(NM_006663.3)(配列番号39)
(40)PR domain containing 5 (PRDM5)(NM_018699.3)(配列番号40)
(41)Protein tyrosine phosphatase, receptor type, C (PTPRC)(NM_002838.4)(配列番号41)
(42)RAB10, member RAS oncogene family (RAB10)(NM_016131.4)(配列番号42)
(43)Ribosomal protein, large, P1 (RPLP1)(NM_001003.2)(配列番号43)
(44)Ras-related GTP binding D (RRAGD)(NM_021244.4)(配列番号44)
(45)Solute carrier family 22, member 15 (SLC22A15)(NM_018420.2)(配列番号45)
(46)Solute carrier family 44, member 1 (SLC44A1)(NM_080546.4)(配列番号46)
(47)Schlafen family member 12 (SLFN12)(NM_018042.4)(配列番号47)
(48)S1 RNA binding domain 1 (SRBD1)(NM_018079.4)(配列番号48)
(49)Tet oncogene family member 2 (TET2)(NM_017628.4)(配列番号49)
(50)Transducin-like enhancer of split 2 (E(sp1) homolog, Drosophila) (TLE2)(NM_003260.4)(配列番号50)
(51)Ubiquitin-conjugating enzyme E2W (putative) (UBE2W)(NM_018299.4)(配列番号51)
(52)Ubiquitination factor E4A (UBE4A)(NM_004788.3)(配列番号52)
(53)Ubiquitin specific peptidase 15 (USP15)(NM_006313.2)(配列番号53)
(54)WD repeat and SOCS box containing 1 (WSB1)(NM_015626.8)(配列番号54)
(55)Zinc finger E-box binding homeobox 2 (ZEB2)(NM_014795.3)(配列番号55)
(56)Zinc metallopeptidase (STE24 homolog, S. cerevisiae) (ZMPSTE24)(NM_005857.4)(配列番号56)
上記56個の遺伝子(1)~(56)の塩基配列をそれぞれ配列表の配列番号1~56に示す。
(ii)CA-19-9の測定
CA-19-9は、生体試料中に含まれるものを免疫学的測定法で測定すればよい。
2.膵臓癌の検出
本発明の方法により、被験体が膵臓癌と診断するための診断補助薬として活用できる。
判別式I:intercept + Σ(beta i × X i)
[式Iにおいて、intercept は定数、beta iは遺伝子セットAの56個の遺伝子のi番目の遺伝子に対する係数、X iは遺伝子セットAの56個の遺伝子のi番目の遺伝子の標準化Ct値であり、Σは遺伝子セットAの56個の遺伝子のそれぞれの遺伝子のbeta × Xを合計することを示す。]
56個の遺伝子セットAについて上記の式Iにそれぞれの遺伝子のCt値を入れ計算し、数値を算出すればよい。算出した値は、Pとして以下の判別式IIに用いる。
判別式II:-2.9448 + (0.0090864 x P) + (0.9329593 x Loge C)
算出された最終判定値Zが正の場合、すなわち最終判定値が0を超える場合に膵臓癌が陽性、負の場合に膵臓癌が陰性であると判定することができる。ここで、膵臓癌が陽性であるとは、膵臓癌に罹患していると判定することができることをいう。
遺伝子セットAのintercept: -298.018
(1)被験体より採取した末梢血細胞よりmRNAを抽出する。
(2)遺伝子セットAの56個の遺伝子をPCRにより増幅し、Ct(Cycle threshold) 値を得て、GAPDH等のハウスキーピング遺伝子のCt値により標準化し、標準化Ct値を得る。
(3)遺伝子セットAについては、遺伝子セットAの各遺伝子の標準化Ct値を判別式Iに代入しP値を求める;
判別式I:intercept + Σ(beta i × X i)
[式Iにおいて、intercept は定数、beta iは遺伝子セットAの56個の遺伝子のi番目の遺伝子に対する係数、X iは遺伝子セットAの56個の遺伝子のi番目の遺伝子の標準化Ct値であり、Σは遺伝子セットAの56個の遺伝子のそれぞれの遺伝子のbeta × Xを合計することを示す。]
(4)被験体より採取した生体試料中のCA19-9を測定しC値とし、該C及び(3)のP値を判別式IIに代入する。
(5)判別式II = -2.9448 + (0.0090864 x P) + (0.9329593 x Loge C)により最終判定値Zを求める。Zが正の場合は膵癌陽性、負の場合は陰性と判定する。(5)の工程は、遺伝子セットAの各遺伝子の標準化Ct値およびCA19-9測定値を判別式に代入し、膵臓癌が陽性であるか、陰性であるかの判断を補助するための値を算出する工程である。
(a) 被験体の遺伝子発現プロファイルに関するデータを入力する手段、ここで入力される遺伝子発現プロファイルに関するデータとは、例えば、各遺伝子における標準化Ct値等の各遺伝子の発現レベルを示すデータと同時測定したCA19-9値である;
(b) 構築した判別式を記憶している記憶手段、
(c) (a)の入力手段を用いて入力したデータを(b)の記憶手段に記憶されている判別式に適用して、膵臓癌の病態の決定を行うためのデータ処理手段を含むシステムである。
膵臓癌54例、慢性膵炎22例、IPMN25例、健常人103例を被験体として用いた。
被験体より採取した末梢血細胞からmRNAを抽出し、遺伝子セットAの56個の遺伝子の遺伝子発現解析をリアルタイムPCRにより行った。
パクスジーンRNA採血管(日本ベクトン・ディッキンソン株式会社 医療機器製造販売認証番号:218AFBZX00014000)を用いて、被験体より末梢血液を採取した。
RNA抽出及びハイブリダイゼーション
パクスジーンRNA採血管よりPAXgene Blood RNA Kit(PreAnalytiX GmbH,Hombrechtikon,Switzerland)を用いて、プロトコールにしたがってRNAを抽出した。
遺伝子セットAの56個の遺伝子を使用し、リアルタイムPCRにて発現解析を行った。
被験体より血清を採取して、以下の試薬及び装置を用いてCA19-9の測定値を用いた。単位はU/mLであった。得られた測定値をCとした。
試薬:ケミルミACS Centaur CA19-9II
装置:ADVIA Centaur XP メーカー:シーメンスヘルスケアダイアグノスティクス
測定原理:化学発光免疫測定法(CLIA法)を同時測定し、その測定値を求めた。
P値の算出
遺伝子セットAの56個の遺伝子の標準化Ct値より以下の判別式Iを用いて、P値を得た。
判別式I:intercept + Σ(beta i × X i)
[式Iにおいて、intercept は定数、beta iは遺伝子セットAの56個の遺伝子のi番目の遺伝子に対する係数、X iは遺伝子セットAの56個の遺伝子のi番目の遺伝子の標準化Ct値であり、Σは遺伝子セットAの56個の遺伝子のそれぞれの遺伝子のbeta × Xを合計することを示す。]
図1にC値(CA19-9の測定値)及びP値(遺伝子解析結果による判別式の算出値)の相関を示す。
CA19-9の測定値をC、遺伝子セットAの判別式Iによる算出値をPとし、以下の判別式IIにより最終判定値Zを求めた。
判別式II = -2.9448 + (0.0090864 x P) + (0.9329593 x Loge C)
最終判定値Zが正の場合は膵臓癌陽性、負の場合は陰性と判定する。
Claims (2)
- 被験体における以下の(1)~(56)の56個の遺伝子セットAの56個の遺伝子の発現レベルを、被験体の末梢血細胞のmRNAを用いて、遺伝子セットAの56個の遺伝子の塩基配列からなるポリヌクレオチド又はその一部配列を含むポリヌクレオチドをターゲットとした定量PCRにより測定し、該56個の遺伝子の発現レベルとCA19-9値の測定値に基づいて膵臓癌の検出を補助する方法であって、以下の工程を含む、方法:
(i)被験体より採取した末梢血細胞よりmRNAを抽出する工程;
(ii)遺伝子セットAの56個の遺伝子をPCRにより増幅し、Ct(Cycle threshold)値を得て、GAPDH等のハウスキーピング遺伝子のCt値により標準化し、標準化Ct値を得て、得られた標準化Ct値より以下の判別式Iを用いてP値を算出する工程
判別式I: intercept + Σ (beta i × X i)
[式において、interceptは-298.018であり、beta iは遺伝子セットAの56個の遺伝子のi番目の遺伝子に対する係数であって下のセットAの表に示す値であり、X iは遺伝子セットAの56個の遺伝子のi番目の遺伝子の標準化Ct値であり、Σは遺伝子セットAの56個の遺伝子のそれぞれの遺伝子のbeta × Xを合計することを示す。
]
;
(iii)被験体より採取した血清中のCA19-9を測定し、得られたCA19-9の測定値をC値とし、P値とC値を以下の判別式IIに代入し、最終判定値Zを得る工程、ここでC値の単位はU/mLである、
判別式II:-2.9448 + (0.0090864 x P) + (0.9329593 x Loge C);
(iv)最終判定値Zが0より大きい場合に膵臓癌が陽性であると判定する工程:
遺伝子セットA
(1)Abhydrolase domain containing 3 (ABHD3)
(2)Abl-interactor 1 (ABI1)
(3)Acyl-CoA synthetase long-chain family member 3 (ACSL3)
(4)Aldo-keto reductase family 1, member B1 (aldose reductase) (AKR1B1)
(5)ATPase, Class VI, type 11B (ATP11B)
(6)UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 5 (B3GNT5)(7)BTB and CNC homology 1, basic leucine zipper transcription factor 1 (BACH1)
(8)Chromosome 11 open reading frame 2 (C11orf2)
(9)Chromosome 2 open reading frame 81 (C2orf81)
(10)Cyclin Y-like 1 (CCNYL1)
(11)Centromere protein N (CENPN)
(12)Complement factor H-related 3 (CFHR3)
(13)C-type lectin domain family 4, member D (CLEC4D)
(14)Collagen, type XVII, alpha 1 (COL17A1)
(15)Cytochrome b5 reductase 4 (CYB5R4)
(16)DENN/MADD domain containing 1B (DENND1B)
(17)Enoyl CoA hydratase domain containing 3 (ECHDC3)
(18)Ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1)
(19)Family with sequence similarity 198, member B (FAM198B)
(20)Family with sequence similarity 49, member B (FAM49B)
(21)Fatty acyl CoA reductase 1 (FAR1)
(22)Fibrinogen-like 2 (FGL2)
(23)Fibronectin type III domain containing 3B (FNDC3B)
(24)Fucose-1-phosphate guanylyltransferase (FPGT)
(25)UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 4 (GalNAc-T4) (GALNT4)
(26)HEAT repeat containing 5A (HEATR5A)
(27)HIV-1 Tat interactive protein 2, 30kDa (HTATIP2)
(28)Interferon gamma receptor 1 (IFNGR1)
(29)IKBKB interacting protein (IKBIP)
(30)Lactate dehydrogenase A (LDHA)
(31)Lysophosphatidic acid receptor 6 (LPAR6)
(32)Membrane-bound transcription factor peptidase, site 2 (MBTPS2)
(33)Minichromosome maintenance complex binding protein (MCMBP)
(34)Mesoderm induction early response 1 homolog (Xenopus laevis) (MIER1)(35)Nuclear factor (erythroid-derived 2)-like 2 (NFE2L2)
(36)Oligonucleotide/oligosaccharide-binding fold containing 2A (OBFC2A)
(37)Oxysterol binding protein-like 8 (OSBPL8)
(38)Peptidylprolyl isomerase H (cyclophilin H) (PPIH)
(39)Protein phosphatase 1, regulatory (inhibitor) subunit 13 like (PPP1R13L)
(40)PR domain containing 5 (PRDM5)
(41)Protein tyrosine phosphatase, receptor type, C (PTPRC)
(42)RAB10, member RAS oncogene family (RAB10)
(43)Ribosomal protein, large, P1 (RPLP1)
(44)Ras-related GTP binding D (RRAGD)
(45)Solute carrier family 22, member 15 (SLC22A15)
(46)Solute carrier family 44, member 1 (SLC44A1)
(47)Schlafen family member 12 (SLFN12)
(48)S1 RNA binding domain 1 (SRBD1)
(49)Tet oncogene family member 2 (TET2)
(50)Transducin-like enhancer of split 2 (E(sp1) homolog, Drosophila) (TLE2)
(51)Ubiquitin-conjugating enzyme E2W (putative) (UBE2W)
(52)Ubiquitination factor E4A (UBE4A)
(53)Ubiquitin specific peptidase 15 (USP15)
(54)WD repeat and SOCS box containing 1 (WSB1)
(55)Zinc finger E-box binding homeobox 2 (ZEB2)
(56)Zinc metallopeptidase (STE24 homolog, S. cerevisiae) (ZMPSTE24)。 - 被験体の遺伝子の発現レベルを、被験体の末梢血細胞のmRNAを用いて測定する、請求項1記載の方法。
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Title |
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Cancer Sci.,2019年,Vol. 110,p. 1364-1388 |
酒井佳夫、金子周一,膵癌の新たな血液バイオマーカーに対する前向き医師主導臨床性能試験,日本消化器病学会雑誌,2020年,第117巻臨時増刊号,p. A63,S9-13 |
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