JP6984862B2 - 血中ケモカインをマーカーとして用いた大腸癌の検出 - Google Patents
血中ケモカインをマーカーとして用いた大腸癌の検出 Download PDFInfo
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[1] 被験体より採取した血液中のMIP-1α及び/又はEotaxinを測定することを含む、大腸癌を検出する方法。
[2] 被験体より採取した血液中のMIP-1α及びEotaxinを測定することを含む、[1]の大腸癌を検出する方法。
[3] 被験体の血液中のMIP-1α濃度が健常人の血液中のMIP-1α濃度よりも高いか、あるいは被験体の血液中のEotaxin濃度が健常人の血液中のEotaxin濃度よりも高い場合に、被験体が大腸癌に罹患していると判断する、[1]又は[2]の大腸癌を検出する方法。
[4] 被験体の血液中のMIP-1α濃度が健常人の血液中のMIP-1α濃度よりも高く、かつ被験体の血液中のEotaxin濃度が健常人の血液中のEotaxin濃度よりも高い場合に、被験体が大腸癌に罹患していると判断する、[1]又は[2]の大腸癌を検出する方法。
[5] 被験体の血液中のMIP-1α濃度が35pg/mL以上であるか、又はEotaxin濃度が150pg/mL以上である場合に、被験体が大腸癌に罹患していると判断する、[1]又は[2]の大腸癌を検出する方法。
[6] 被験体の血液中のMIP-1α濃度が35pg/mL以上であり、かつEotaxin濃度が150pg/mL以上である場合に、被験体が大腸癌に罹患していると判断する、[1]又は[2]の大腸癌を検出する方法。
[7] [1]〜[6]のいずれかの大腸癌を検出する方法に用いる検査試薬であって、抗MIP-1α抗体及び/又は抗Eotaxin抗体を含む検査試薬。
(1) MIP-1α(Macrophage inflammatory protein -1α)及び/又はEotaxin(エオタキシン)をマーカーとして用いての大腸癌の検出
本発明は、ケモカインの1種であるMIP-1α(Macrophage inflammatory protein -1α)及び/又はEotaxin(エオタキシン)をマーカーとして用いて、大腸癌を検出する方法である。
血中Eotaxin濃度の増加に相関してCD4陽性細胞において発現が亢進又は抑制される遺伝子の存在が確認されており、それらの遺伝子の発現の亢進または抑制を指標にして大腸癌を検出することができる。
図3−1及び3−2においては、遺伝子を機能ごとに分けて挙げている。
血中Eotaxin濃度の増加に相関してCD4陽性細胞において発現が亢進する遺伝子
1 Immune response_Phagocytosis
ITGB2, Syk, IL-15, RhoA, Myosin I, C/EBP, Dectin-1, Fc gamma RII beta, ILT4, MSN (moesin), ERM proteins, SHPS-1, Fc epsilon RI gamma, MSR1, MANR, Lyn, PLC-gamma 2, IL-15RA, Btk, ILT2, Hck, TLR4, MARCO, MARCKS, MLCK, PLC-gamma, gp91-phox, p40-phox, PAK1, p67-phox, FGR, Fc alpha receptor, Fc gamma RII alpha
2 Cell adhesion_Platelet aggregation
ITGB2, Syk, GAB2, PLA2, RhoA, Thrombospondin 1, G-protein beta/gamma, COX-1 (PTGS1), Fc epsilon RI gamma, c-Src, ENP1, THAS, cPLA2, PTAFR, Lyn, PLC-gamma 2, PKA-reg (cAMPdependent), GP-IX, P2Y12, Gab, G-protein alpha-i family, G-protein alpha-i2, P2X1, MLCK, PLC-gamma, CD36, VAV-2
3 Cell adhesion_Amyloid proteins
RhoA, FZD1, Nicastrin, NOTCH2, APLP2 active fragment, G-protein beta/gamma, Jagged1, Nidogen, p120-catenin, Tcf(Lef), c-Src, Presenilin 2, FZD2, FZD5, Notch, Presenilin 1, Alpha-catenin, APLP2 precursor, Cathepsin D, MALS, Frizzled, ADAM9, PKC, PAK1, Plakoglobin, Presenilin
4 Immune response_Antigen presentation
CIITA, ICAM1, MHC class II beta chain, CD1b, HLADPA1, CD1d, HLA-DQA1, JAK2, HA2Z, Fc epsilon RI gamma, IP-30, HLA-DM, HLA-DRB1, CD1a, Cathepsin S, LFA-3, MHC class II, HLA-DQB1, HLA-DRA1, HLA-DPB1, HLA-DRB4, CD86, CD74, RING6
5 Proliferation_Positive regulation cell proliferation
p21, HGF, RhoG, Beta-arrestin1, GAB2, Fra-1, RhoA, Galpha(i)- specific peptide GPCRs, JAK2, MTG16 (CBFA2T3), c-Src, VEGF-A, RasGRP4, PKA-reg (cAMP-dependent), G-protein alpha-15, TCIRG1 (Atp6i), CCR1, G-protein alpha-i family, M-CSF receptor, G-protein alpha-i2, CSDA, MLCK, c-Fes, FLT3, PAK1
6 Chemotaxis
ITGB2, Syk, C5aR, Fra-1, GRO-2, Prokineticin 2, PD-ECGF (TdRPase), IL-1 beta, Galpha(i)-specific peptide GPCRs, PLAUR (uPAR), MIG, Integrin, VEGF-A, PTAFR, CCR1, G-protein alpha-i family, Galpha(q)-specific peptide GPCRs, PLD1
7 Inflammation_IFN-gamma signaling
CIITA, p21, ITGB2, IL-15, IL-18, ICAM1, PKC-delta, K12, JAK2, MIG, c-Src, PLC-gamma 2, TLR4, PLC-gamma, Fc alpha receptor
8 Apoptosis_Anti-apoptosis mediated by external signals via NF-kB
IL-15, MyD88, G-protein beta/gamma, TNF-R2, VEGF-A, CD30(TNFRSF8), CSF2RA, PKA-reg (cAMP-dependent), IL-15RA, G-protein alpha-i family, TLR4, Bcl-3, TL1A(TNFSF15), APRIL(TNFSF13), BAFF(TNFSF13B)
9 Inflammation_Neutrophil activation
ITGB2, C5aR, PLA2, ICAM1, GRO-2, RhoA, PKC-delta, G-protein beta/gamma, TNF-R2, Galpha(i)-specific peptide GPCRs, Syntaxin 7, cPLA2, Btk, G-protein alpha-15, G-protein alpha-i family, G-protein alpha-i2, PA24A, gp91-phox, ALOX5, p40-phox, PAK1, p67-phox, PLD1
10 Inflammation_IL-4 signaling
HLADPA1, HLA-DQA1, JAK2, MHC class II, Bax, HLA-DQB1, HLADRA1, HLA-DPB1, HLA-DRB4, CD86, CD74, c-Fes, CD13, IL13RA1, Fc gamma RII alpha
1 Proteolysisi ECM remodelin
Collagen XIV, Tenascin-C, NEPH2, MMP-16, Protein C inhibitor, Serpin B12, COL18A1, Kallikrein 2, Trypsin II, Aggrecanase-1
2 Neurophysiological process_Transmission of nerve impulse
L-type Ca(II) channel, alpha 1C subunit, GABA-A receptor gamma-2 subunit, KCC2, mGluR3, Galpha(i)-specific peptide GPCRs, mGluR1, Galpha(q)-specific metabotropic glutamate GPCRs, Ionotropic glutamate receptor, Galpha(i)-specific metabotropic glutamate GPCRs, GluR6, Galpha(i)-specific amine GPCRs, CHT1, RIN, G-protein alpha-s, Kainate receptor
3 Reproduction_Gonadotropin regulation
L-type Ca(II) channel, alpha 1C subunit, GABA-A receptor gamma-2 subunit, mGluR3, mGluR1, Galpha(q)-specific metabotropic glutamate GPCRs, Ionotropic glutamate receptor, Galpha(i)- specific metabotropic glutamate GPCRs, Secretogranin 1, Protein kinase G1, Adenylate cyclase, G-protein alpha-s, Protein kinase G, Kainate receptor
4 Development_Blood vessel morphogenesis
PDE, Galpha(i)-specific peptide GPCRs, PDE7A, Endomucin, Galpha(q)-specific amine GPCRs, Galpha(i)-specific amine GPCRs, Protein kinase G1, Galpha(q)-specific peptide GPCRs, COL18A1, Tissue kallikreins, Neuropilin-1, G-protein alpha-s, Protein kinase G, Transferrin
5 Reproduction_Spermatogenesis, motility and copulation
PDGF receptor, MFGE8, IGF-1 receptor, Ropporin, MSK1, S5AR2, BBS2, Tissue kallikreins, BMP2, Kallikrein 2, SOX5, CREM (activators), ZFP37, PDGF-R-alpha
6 Proteolysis_Connective tissue degradation
Trypsin, Tenascin-C, MMP-16, Protein C inhibitor, Serpin B12, Tissue kallikreins, Kallikrein 2, Trypsin II, Aggrecanase-1
7 Development_Neurogenesis in general
WNT4, RET, CHRM, Neuromodulin, WNT7A, WNT, Galpha(q)-specific amine GPCRs, Galpha(i)- specific amine GPCRs, HDAC7, ACM3, SOX8, SOX14
8 Development_Cartilage development
TR-alpha, Noggin, COL1A2, BMP2, SOX5, Aggrecanase-1
9 Reproduction_Male sex differentiation
AP-2A, PDGF receptor, Olfactory receptor, RET, IGF-1 receptor, MSK1, S5AR2, HSF2, BMP2, SOX5, CREM (activators), ZFP37, PDGF-R-alpha
10 Reproduction_GnRH signaling pathway
GABA-A receptor gamma-2 subunit, mGluR3, mGluR1, Galpha(q)-specific metabotropic glutamate GPCRs, Ionotropic glutamate receptor, Galpha(i)-specific metabotropic glutamate GPCRs, Protein kinase G1, G-protein alpha-s, Protein kinase G, Kainate receptor
大腸癌患者5名,健常者7名について,血中ケモカイン濃度と大腸癌発症との関連を網羅的に解析した。
図2に大腸癌患者(Co)と健常人(N)の血清中MIP-1α濃度(右)とEotaxin濃度(左)を示す。
方法
各被検者の末梢血から、MACS磁気分離システム(ミルテニバイオテク社)を用いて、CD4陽性細胞をソーティング回収した。得られたCD4陽性細胞からRNAを抽出してマイクロアレイ法(Whole Human Genome DNA microarray 4x44K,アジレント社)を用いて遺伝子発現解析をした。
Claims (3)
- 被験体より採取した血液中のMIP-1α及びEotaxinを測定することを含む、大腸癌を検出するための補助的データを取得する方法であって、被験体の血液中のMIP-1α濃度が健常人の血液中のMIP-1α濃度よりも高く、かつ被験体の血液中のEotaxin濃度が健常人の血液中のEotaxin濃度よりも高い場合に、被験体が大腸癌に罹患していると判断するための、大腸癌を検出するための補助的データを取得する方法。
- 被験体の血液中のMIP-1α濃度が35pg/mL以上であり、かつEotaxin濃度が150pg/mL以上である場合に、被験体が大腸癌に罹患していると判断するための、請求項1記載の大腸癌を検出するための補助的データを取得する方法。
- 請求項1又は2に記載の大腸癌を検出するための補助的データを取得する方法に用いる検査試薬であって、抗MIP-1α抗体及び/又は抗Eotaxin抗体を含む検査試薬。
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