Methods of detecting cancer
This invention provides a set of biological markers that are useful for detecting cancer. This invention further provides methods of using those biological markers for the diagnosis, prognosis, or monitoring of cancer.
1. A method for detecting the presence or absence of prostate, head, or neck cancer in a subject, the method comprising the steps of:
a) measuring the levels of four or more markers selected from the group consisting of P2RY10, TNFAIP3, CXCR1, DNAJB1, CHI3L1, KIAA1324, CEACAM1, TIPARP, ALPL, SLC38A1, PBXIP1, DUSP16, TNF, ZDHHC18, DUSP5, PI3, PHOSPHO1, MPZL3, CXCR2, FAIM3, MAPK13, ROPN1L, TSC22D3, GPR97, FAM46C, HBEGF, EREG, SNAP, RAB20, GPR183, NR4A1, CCRN4L, ICOSLG, N4BP1, SDCBP, SMCHD1, GZF1, SNAI1 MME, MMP9, KIAA0040, KLF2, ZEB1, NR4A3, ATF4, XPO6, SLC6, LRP10, PELI, OLR1, CYP4F, FAM129A, C12orf35, SLC12A6, SMCHD1, BCL6, ZNF200, TMEM45B, SEC14L2, IFITM1, IL18RAP, GNG10, TNFRSF10C, IRF1, EGLN1, HCG27, OSM, HIST1H3A, NSFL1C, ELOVL5, PIK3R1, SYNE2, JUNB, RHOG, VEGFA, FRAT1, UBE2J1, PDE4D, MS4A1, MMP25, FAS, SNRK, CD83, HIST2H2BA, MANSC1, BAZ1A, SPATA13, MGAT1, MED31, TNFRSF21, C17orf71, TRIB3, SNORD56B, WIPI1, ANXA3, HSPC159, RHOU, ATP6V1B2, GKS, and GRASP in a population of the subject's macrophage cells OR measuring the levels of four or more markers selected from the group consisting of EEF1A1, RPL23A, RPL14, RPL3, RL10, PTMA, RPS13, RPL18A, RPL8, RPS2, GLTSCR2, RPL13A, RPL18, RPS2, SLC25A6, RPL15, TCF12, EEF1G, RPL10, RPS28, RPS8, SNAPC3, GNB2L1, RPS17, RPL5, RPSI5, RPS4X, RPL27, RPL6, RPL35, RPL35A, RPL12, RPLP0, RPL39, RPL7, MPV17, YBX1, RPL13AP5, ILF2, RPS2, RPL12, TMSB10, RPL39, CD52, RPL, RPL9, RPL18A, RPL12, DNAJC15, RPL7, HLA-DPB1, RPLP1, ATXN10, CCDC6, HLA-DPB1, ANXA6, RPL38, HLA-DPB1, APEX1, VPS45, CD74, RPS14, NDUFA12, RPL7A, IL10RA, RPS15A, ALG3, MBNL3, FBL, RPLP0, ECH1, RCC2, TRIM44, LOC138412, ZMYM4, CYB5B, TCERG1, RPS3A, FXYD5, HLA-DRB3, and AHNAK in a population of the subject's neutrophil cells;
b) measuring the levels of the four or more selected markers in a population of the subject's non-phagocytic cells; and
c) identifying a difference between the measured levels of the four or more selected markers in steps a) and b);
wherein the identified difference is indicative of the presence or absence of prostate, head, or neck cancer in the subject.
2. The method of claim 1 , further comprising measuring at least one standard parameter associated with prostate cancer.
3. The method of claim 2 , wherein the standard parameter is selected from the group consisting of tumor stage, tumor grade, tumor size, tumor visual characteristics, tumor growth, tumor thickness, tumor progression, tumor metastasis tumor distribution within the body, odor, molecular pathology, genomics, and tumor angiograms.
4. The method of claim 1 , wherein the non-phagocytic cells are isolated from a bodily fluid sample, tissues, or cells of the subject.
5. The method of claim 1 , wherein the non-phagocytic cells are T cells, B cells, null cells, basophils, or mixtures thereof.
6. The method of claim 1 , wherein the macrophage cells are isolated from a bodily fluid sample, tissues, or cells of the subject.
7. The method of claim 1 , wherein the neutrophil cells are isolated from a bodily fluid sample, tissues, or cells of the subject.
8. The method of claim 1 , wherein the macrophage cells, neutrophil cells and non-phagocytic cells are isolated from a bodily fluid sample, tissues, or cells of the subject.
9. The method of claim 8 , wherein the bodily fluid sample is blood, urine, stool, saliva, lymph fluid, cerebrospinal fluid, synovial fluid, cystic fluid, ascites, pleural effusion, fluid obtained from a pregnant woman in the first trimester, fluid obtained from a pregnant woman in the second trimester, fluid obtained from a pregnant woman in the third trimester, maternal blood, amniotic fluid, chorionic villus sample, fluid from a preimplantation embryo, maternal urine, maternal saliva, placental sample, fetal blood, lavage and cervical vaginal fluid, interstitial fluid, or ocular fluid.
10. The method of claim 1 , comprising measuring the levels of five or more markers selected from the group consisting of P2RY10, TNFAIP3, CXCR1, DNAJB1, CHI3L1, KIAA1324, CEACAM1, TIPARP, ALPL, SLC38A1, PBXIP1, DUSP16, TNF, ZDHHC18, DUSP5, PI3, PHOSPHO1, MPZL3, CXCR2, FAIM3, MAPK13, ROPN1L, TSC22D3, GPR97, FAM46C, HBEGF, EREG, SNAP, RAB20, GPR183, NR4A1, CCRN4L, ICOSLG, N4BP1, SDCBP, SMCHD1, GZF1, SNAI1, MME, MMP9, KIAA0040, KLF2, ZEB1, NR4A3, ATF4, XPO6, SLC6, LRP10, PELI, OLR1, CYP4F, FAM129A, C12orf35, SLC12A6, SMCHD1, BCL6, ZNF200, TMEM45B, SEC14L2, IFITM1, IL18RAP, GNG10, TNFRSF10C, IRF1, EGLN1, HCG27, OSM, HIST1H3A, NSFL1C, ELOVL5, PIK3R1, SYNE2, JUNB, RHOG, VEGFA, FRAT1, UBE2J1, PDE4D, MS4A1, MMP25, FAS, SNRK, CD83, HIST2H2BA, MANSC1, BAZ1A, SPATA13, MGAT1, MED31, TNFRSF21, C17orf71, TRIB3, SNORD56B, WIPI1, ANXA3, HSPC159, RHOU, ATP6V1B2, GKS, and GRASP or measuring the levels of five or more markers selected from the group consisting of EEF1A1, RPL23A, RPL14, RPL3, RL10, PTMA, RPS13, RPL18A, RPL8, RPS2, GLTSCR2, RPL13A, RPL18, RPS2, SLC25A6, RPL15, TCF12, EEF1G, RPL10, RPS28, RPS8, SNAPC3, GNB2L1, RPS17, RPL5, RPSI5, RPS4X, RPL27, RPL6, RPL35, RPL35A, RPL12, RPLP0, RPL39, RPL7, MPV17, YBX1, RPL13AP5, ILF2, RPS2, RPL12, TMSB10, RPL39, CD52, RPL, RPL9, RPL18A, RPL12, DNAJC15, RPL7, HLA-DPB1, RPLP1, ATXN10, CCDC6, HLA-DPB1, ANXA6, RPL38, HLA-DPB1, APEX1, VPS45, CD74, RPS14, NDUFA12, RPL7A, IL10RA, RPS15A, ALG3, MBNL3, FBL, RPLP0, ECH1, RCC2, TRIM44, LOC138412, ZMYM4, CYB5B, TCERG1, RPS3A, FXYD5, HLA-DRB3, and AHNAK.
11. The method of claim 1 , comprising measuring the levels of ten or more markers selected from the group consisting of P2RY10, TNFAIP3, CXCR1, DNAJB1, CHI3L1, KIAA1324, CEACAM1, TIPARP, ALPL, SLC38A1, PBXIP1, DUSP16, TNF, ZDHHC18, DUSP5, PI3, PHOSPHO1, MPZL3, CXCR2, FAIM3, MAPK13, ROPN1L, TSC22D3, GPR97, FAM46C, HBEGF, EREG, SNAP, RAB20, GPR183, NR4A1, CCRN4L, ICOSLG, N4BP1, SDCBP, SMCHD1, GZF1, SNAI1, MME, MMP9, KIAA0040, KLF2, ZEB1, NR4A3, ATF4, XPO6, SLC6, LRP10, PELI, OLR1, CYP4F, FAM129A, C12orf35, SLC12A6, SMCHD1, BCL6, ZNF200, TMEM45B, SEC14L2, IFITM1, IL18RAP, GNG10, TNFRSF10C, IRF1, EGLN1, HCG27, OSM, HIST1H3A, NSFL1C, ELOVL5, PIK3R1, SYNE2, JUNB, RHOG, VEGFA, FRAT1, UBE2J1, PDE4D, MS4A1, MMP25, FAS, SNRK, CD83, HIST2H2BA, MANSC1, BAZ1A, SPATA13, MGAT1, MED31, TNFRSF21, C17orf71, TRIB3, SNORD56B, WIPI1, ANXA3, HSPC159, RHOU, ATP6V1B2, GKS, and GRASP or measuring the levels of ten or more markers selected from the group consisting of EEF1A1, RPL23A, RPL14, RPL3, RL10, PTMA, RPS13, RPL18A, RPL8, RPS2, GLTSCR2, RPL13A, RPL18, RPS2, SLC25A6, RPL15, TCF12, EEF1G, RPL10, RPS28, RPS8, SNAPC3, GNB2L1, RPS17, RPL5, RPSI5, RPS4X, RPL27, RPL6, RPL35, RPL35A, RPL12, RPLP0, RPL39, RPL7, MPV17, YBX1, RPL13AP5, ILF2, RPS2, RPL12, TMSB10, RPL39, CD52, RPL, RPL9, RPL18A, RPL12, DNAJC15, RPL7, HLA-DPB1, RPLP1, ATXN10, CCDC6, HLA-DPB1, ANXA6, RPL38, HLA-DPB1, APEX1, VPS45, CD74, RPS14, NDUFA12, RPL7A, IL10RA, RPS15A, ALG3, MBNL3, FBL, RPLP0, ECH1, RCC2, TRIM44, LOC138412, ZMYM4, CYB5B, TCERG1, RPS3A, FXYD5, HLA-DRB3, and AHNAK.
12. The method of claim 1 , comprising measuring the levels of four or more markers selected from the group consisting of P2RY10, TNFAIP3, CXCR1, DNAJB1, CHI3L1, KIAA1324, CEACAM1, TIPARP, ALPL, SLC38A1, PBXIP1, DUSP16, TNF, ZDHHC18, DUSP5, PI3, PHOSPHO1, MPZL3, CXCR2, FAIM3, MAPK13, ROPN1L, TSC22D3, GPR97, FAM46C, HBEGF, EREG, SNAP, RAB20, GPR183, NR4A1, CCRN4L, ICOSLG, N4BP1, SDCBP, SMCHD1, GZF1, SNAI1, MME, MMP9, KIAA0040, KLF2, ZEB1, NR4A3, ATF4, XPO6, SLC6, LRP10, PELI, OLR1, CYP4F, FAM129A, C12orf35, SLC12A6, SMCHD1, BCL6, ZNF200, TMEM45B, SEC14L2, IFITM1, IL18RAP, GNG10, TNFRSF10C, IRF1, EGLN1, HCG27, OSM, HIST1H3A, NSFL1C, ELOVL5, PIK3R1, SYNE2, JUNB, RHOG, VEGFA, FRAT1, UBE2J1, PDE4D, MS4A1, MMP25, FAS, SNRK, CD83, HIST2H2BA, MANSC1, BAZ1A, SPATA13, MGAT1, MED31, TNFRSF21, C17orf71, TRIB3, SNORD56B, WIPI1, ANXA3, HSPC159, RHOU, ATP6V1B2, GKS, and GRASP and measuring the levels of four or more markers selected from the group consisting of EEF1A1, RPL23A, RPL14, RPL3, RL10, PTMA, RPS13, RPL18A, RPL8, RPS2, GLTSCR2, RPL13A, RPL18, RPS2, SLC25A6, RPL15, TCF12, EEF1G, RPL10, RPS28, RPS8, SNAPC3, GNB2L1, RPS17, RPL5, RPSI5, RPS4X, RPL27, RPL6, RPL35, RPL35A, RPL12, RPLP0, RPL39, RPL7, MPV17, YBX1, RPL13AP5, ILF2, RPS2, RPL12, TMSB10, RPL39, CD52, RPL, RPL9, RPL18A, RPL12, DNAJC15, RPL7, HLA-DPB1, RPLP1, ATXN10, CCDC6, HLA-DPB1, ANXA6, RPL38, HLA-DPB1, APEX1, VPS45, CD74, RPS14, NDUFA12, RPL7A, IL10RA, RPS15A, ALG3, MBNL3, FBL, RPLP0, ECH1, RCC2, TRIM44, LOC138412, ZMYM4, CYB5B, TCERG1, RPS3A, FXYD5, HLA-DRB3, and AHNAK.
13. A method for detecting the presence or absence of a cancer in a subject, the method comprising the steps of:
a) measuring the levels of at least four or more markers selected from the group consisting of P2RY10, TNFAIP3, CXCR1, DNAJB1, CHI3L1, KIAA1324, CEACAM1, TIPARP, ALPL, SLC38A1, PBXIP1, DUSP16, TNF, ZDHHC18, DUSP5, PI3, PHOSPHO1, MPZL3, CXCR2, FAIM3, MAPK13, ROPN1L, TSC22D3, GPR97, FAM46C, HBEGF, EREG, SNAP, RAB20, GPR183, NR4A1, CCRN4L, ICOSLG, N4BP1, SDCBP, SMCHD1, GZF1, SNAI1 MME, MMP9, KIAA0040, KLF2, ZEB1, NR4A3, ATF4, XPO6, SLC6, LRP10, PELI, OLR1, CYP4F, FAM129A, C12orf35, SLC12A6, SMCHD1, BCL6, ZNF200, TMEM45B, SEC14L2, IFITM1, IL18RAP, GNG10, TNFRSF10C, IRF1, EGLN1, HCG27, OSM, HIST1H3A, NSFL1C, ELOVL5, PIK3R1, SYNE2, JUNB, RHOG, VEGFA, FRAT1, UBE2J1, PDE4D, MS4A1, MMP25, FAS, SNRK, CD83, HIST2H2BA, MANSC1, BAZ1A, SPATA13, MGAT1, MED31, TNFRSF21, C17orf71, TRIB3, SNORD56B, WIPI1, ANXA3, HSPC159, RHOU, ATP6V1B2, GKS, and GRASP in a population of the subject's macrophage cells, and
measuring the levels of at least four or more markers selected from the group consisting of EEF1A1, RPL23A, RPL14, RPL3, RL10, PTMA, RPS13, RPL18A, RPL8, RPS2, GLTSCR2, RPL13A, RPL18, RPS2, SLC25A6, RPL15, TCF12, EEF1G, RPL10, RPS28, RPS8, SNAPC3, GNB2L1, RPS17, RPL5, RPSI5, RPS4X, RPL27, RPL6, RPL35, RPL35A, RPL12, RPLP0, RPL39, RPL7, MPV17, YBX1, RPL13AP5, ILF2, RPS2, RPL12, TMSB10, RPL39, CD52, RPL, RPL9, RPL18A, RPL12, DNAJC15, RPL7, HLA-DPB1, RPLP1, ATXN10, CCDC6, HLA-DPB1, ANXA6, RPL38, HLA-DPB1, APEX1, VPS45, CD74, RPS14, NDUFA12, RPL7A, IL10RA, RPS15A, ALG3, MBNL3, FBL, RPLP0, ECH1, RCC2, TRIM44, LOC138412, ZMYM4, CYB5B, TCERG1, RPS3A, FXYD5, HLA-DRB3, and AHNAK in a population of the subject's neutrophil cells;
b) measuring the levels of the at least four or more markers selected from the subject's macrophage cells in a population of the subject's non-phagocytic cells; and
measuring the levels of the at least four or more markers selected from the subject's neutrophil cells in a population of the subject's non-phagocytic cells;
c) identifying a difference between the measured levels of the selected markers in steps a) and b); and
d) identifying a difference between the measured levels or activities of the selected markers in steps a) and b);
wherein the differences identified in c) and d) are indicative of the presence or absence-of the cancer in the subject.