Claims
- 1. A method for predicting the outcome of cancer in a patient, comprising the steps of:
comparing level of expression of at least one RNA transcript or its translation product from a first or a second group of RNA transcripts in a first sample of prostate tissue to level of expression of the transcripts or translation products in a second sample of prostate tissue wherein the first prostate tissue sample is neoplastic and the second prostate tissue sample is a nonmalignant human prostate tissue, wherein the first group of RNA transcripts consists of transcripts of genes selected from the group consisting of SLC14A1-urea transporter (U35735), CYP3AI-cytochrome P-450 (P-450 HFLa) (D00408), KRT5—keratin type II (M21389), P15—protease inhibitor 5 (maspin) (U04313), ATDC—ataxia-telangiectasia group D-associated protein (L24203), TGFB3 (transforming growth factor, beta 3) (X14885), GSTM3 (glutathione transferase M3) (J05459), hKvBeta3 (potassium voltage-gated channel, beta member 3) (L39833), GPM6B (glycoprotein M6B) (U45955), SRPX (sushi-repeat containing protein, X chromosome) (U61374), ROR2 (receptor tyrosine kinase-like orphan receptor 2) (M97639), RBP (retinol binding protein) (X00129), H19 RNA gene (M32053), PLCE (phospholipase C, epsilon) (D42108), MYHI 1 (myosin, heavy polypeptide II, smooth muscle) (D10667), CSTA (cystatin A (stefin A)) (D88422), NELL2 (nel (chicken)-like 2) (D83018), ID4 (inhibitor of DNA binding 4, dominant negative helix-loop-helix protein) (U28368), FGFR1 (fibroblast growth factor receptor 1) (X66945), KCNMBI (potassium large conductance calcium-activated channel, subfamily M, beta member 1) (U25138), CAMK2G (calcium/calmodulin-dependent protein kinase (CaM kinase) II gamma) (U50360), TRPC 1 (transient receptor potential channel 1) (X89066), BRF2 (butyrate response factor 2 (EGF-response factor 2)) (X78992), RARRES2 (retinoic acid receptor responder (tazarotene induced) 2) (U77594), gasl gene (L13698), SERPINFI (serene or cysteine) proteinase inhibitor, clade F (alpha-2 antiplasmin, pigment epithelium derived factor, member 1) (U29953), caveolm-2 (U32114), ETV5 (ets variant gene 5 (ets-related molecule)) (X96381), KIAA0003/ANGPTI (angiopoietm 1) (D13628), MT1L (metallothionein 1L) (X76717), KIAK0002/CCND2 (cyclin D2) (D13639), VCL (vinculin) (M33308), COX7A1 (cytochrome c oxidase subunit Vila polypeptide 1 (muscle)) (M83186), PYGL (phosphorylase, glycogen; liver (Hers disease, glycogen storage disease type VI)) (M14636), SLC2A5 (solute carrier family 2 (facilitated glucose transporter), member 5) (M55531), annexin VI (p68) (Y00097), DRAL (L42176), DPYSL3 (dibydropyrimidinaselike 3) (D78014), A-362G6.1 (hypothetical protein A-362G6.1) (U95740_rna), TIMP3 (tissue inhibitor of metalloproteinase 3) (D45917), MIG2 (mitogen inducible 2 (Z24725), SDF1 (stromal cell-derived factor 1) (U19495), KIAA0025 (KIM0025 gene product; MMS-inducible gene) (D14695), PRNP (prion protein (p27-30)) (X83416), AOX1 (aldehyde oxidase 1) (L11005), PLP2 (proteolipid protein 2 (colonic epithelium-enriched)) (L09604), MT2A (metallothionein 2A) (V00594), RRAS (related RAS viral (r-ras) oncogene homolog) (M14949), and LIP2 (D00017) and wherein the second group of RNA transcripts consists of transcripts of genes selected from the group consisting of Hepsin (X07732), PLAB/Prostate differentiation factor/TGF-P (AB000584), GJB1/gap junction protein (X04325), Neuronal apoptosis inhibitory protein (U19251), TMSNB/NB thymosin β (D82345), Human mRNA KIM00167, partial sequence (D28589), PLA2G7/LDL-phospholipase A2 (U24577), Homeo box c8 protein (M16938), Human carcinoma associated antigen GA733-2 (M93036), HSD17B4/17β-hydroxysteroid dehydrogenase IV (X87176), ALCAM/Activated leucocyte cell adhesion molecule (U30999), Macmarcks (HG1612-HT1612), ERK3 (extracellular signal-regulated kinase) (X80692), RNA polymerase II subunit (hsRPB8) (U37689), NBK apoptotic inducer protein (X89986), PYCR1/Pyrroline 5-carboxylate reductase 1 (M77836), APEX nuclease (D13370), Ring zinc-forger protein (ANF127-xp) (U41315), SLC25A6/Solute carrier family 25, member A6 (J03592), and Arginine-rich protein (M83751); identifying the patient as having a poor outcome when expression of at least one of the first group of RNA transcripts or translation products is found to be lower in the first sample than in the second sample, and expression of at least one of the second group of transcripts or translation products is found to be higher in the first sample than in the second sample.
- 2. The method of claim 1 further comprising the step of comparing transcripts or translation products of at least two of the genes of the first group is performed.
- 3. The method of claim 1 further comprising the step of comparing transcripts or translation products of at least two of the genes of the second group is performed.
- 4. The method of claim 1 further comprising the step of comparing transcripts or translation products of at least five of the genes of the first group is performed.
- 5. The method of claim 1 further comprising the step of comparing transcripts or translation products of at least five of the genes of the second group is performed.
- 6. The method of claim 1 further comprising the step of comparing transcripts or translation products of at least ten of the genes of the first group is performed.
- 7. The method of claim 1 further comprising the step of comparing transcripts or translation products of at least ten of the genes of the second group is performed.
- 8. The method of claim 1 further comprising the step of comparing transcripts or translation products of at least twenty of the genes of the first group is performed.
- 9. The method of claim 1 further comprising the step of comparing transcripts or translation products of at least twenty of the genes of the second group is performed.
- 10. The method of claim 1 further comprising the step of comparing transcripts or translation products of at least thirty of the genes of the first group is performed.
- 11. The method of claim 1 further comprising the step of comparing transcripts or translation products of at least forty-nine of the genes of the first group is performed.
- 12. The method of claim 1 wherein the at least one RNA transcript or its translation product of the first group comprises the transcript of the gene maspin (U04313).
- 13. The method of claim 1 wherein the at least one RNA transcript or its translation product of the second group comprises the transcript of the gene hepsin (X07732).\
- 14. The method of claim 1 further comprising the step of categorizing the patient as having a poor outcome when expression of the at least one RNA transcript or translation product of the first group is found to be at least 1.5 fold lower in the first tissue sample relative to the second tissue sample.
- 15. The method of claim 1 further comprising the step of comparing a transcript or translation product of the first group, said transcript or translation product being of a gene selected from the group consisting of SLC14A1-urea transporter (U35735), CYP3A1-cytochrome P-450 (P-450 HFLa) (D00408), KRT5—keratin type 11(M21389), P15—protease inhibitor 5 (maspin) (U04313), ATDC—ataxia-telangiectasia group D-associated protein (L24203), TGFB3 (transforming growth factor, beta 3) (X14885), GSTM3 (glutathione transferase M3) (J05459), hKvBeta3 (potassium voltage-gated channel, beta member 3) (L39833), GPM6B (glycoprotein M6B) (U45955), SRPX (sushi-repeat-containing protein, X chromosome) (U61374), ROR2 (receptor tyrosine kinase-like orphan receptor 2) (M97639), RBP (retinol binding protein) (X00129), H19 RNA gene (M32053), PLCE (phospholipase C, epsilon) (D42108), MYH11 (myosin, heavy polypeptide II, smooth muscle) (D10667), CSTA (cystatin A (stefin A)) (D88422), NELL2 (nel (chicken)-like 2) (D83018), ID4 (inhibitor of DNA binding 4, dominant negative helix-loop-helix protein) (U28368), FGFR1 (fibroblast growth factor receptor 1) (X66945), KCNMB 1 (potassium large conductance calcium-activated channel, subfamily M, beta member 1) (U25138), and CAMK2G (calcium/calmodulin-dependent protein kinase (CaM kinase) II gamma) (U50360).
- 16. The method of claim 15 further comprising the step of identifying the patient as having a poor outcome when expression of the at least one RNA transcript or translation product of the first group is found to be at least 4 fold lower in the first tissue sample relative to the second tissue sample.
- 17. The method of claim 1 further comprising the step of identifying the patient as having a poor outcome when expression of the at least one RNA transcript or translation product of the second group is found to be at least 1.5 fold higher in the first tissue sample relative to the second tissue sample.
- 18. The method of claim 1 further comprising the step of comparing transcript or translation product of the second group, said transcript or translation product being of a gene selected from the group consisting of Hepsin (X07732), PLAB/Prostate differentiation factor/TGF-β (AB000584), GJB1/gap junction protein (X04325), Neuronal apoptosis inhibitory protein (U19251), TMSNB/NB thymosin β (D82345), Human mRNA KIAA00167, partial sequence (D28589), and PLA2G7/LDL-phospholipase A2 (U24577).
- 19. The method of claim 18 further comprising the step of categorizing the patient as having a poor outcome when expression of the at least one RNA transcript or translation product of the second group is found to be at least four fold higher in the first tissue sample relative to the second tissue sample.
- 20. The method of claim 1 further comprising the step of comparing the level of expression of at least one RNA transcript of the fast group in the first sample to the level of expression of said transcript in the second sample.
- 21. The method of claim 1 further comprising the step of determining the level of expression of RNA transcripts using an array of nucleic acid molecules.
- 22. The method of claim 1 further comprising the step of comparing the level of expression of at least one RNA transcript of the second group in the first sample to the level of expression of said transcript in the second sample.
- 23. The method of claim 1 further comprising the step of comparing transcripts or translation products of at least two genes in each of said first and said second groups.
- 24. The method of claim 1 further comprising the step of comparing transcripts or translation products of at least five genes in each of said first and said second groups.
- 25. The method of claim 1 further comprising the step of comparing transcripts or translation products of at least ten genes in each of said first and said second groups.
- 26. The method of claim 1 further comprising the step of comparing transcripts or translation products of at least twenty genes in each of said first and said second groups.
- 27. The method of claim 1 further comprising the step of comparing at least thirty transcripts or translation products in the first group and twenty transcripts or translation products in the second groups.
- 28. The method of claim 1 further comprising the step of comparing at least forty transcripts or translation products in the first group and twenty transcripts or translation products in the second group.
- 29. The method of claim 1 further comprising the step of comparing at least forty-nine transcripts or translation products in the first group and twenty transcripts or translation products in the second group.
- 30. The method of claim 1 further comprising the step of identifying the patient as having a poor outcome when expression of at least one RNA transcript or translation product of the first group is found to be at least 1.5-fold lower in the first sample relative to the second sample, and the expression of at least one of RNA transcript or translation product of the second group is found to be at least 1.5-fold higher in the first sample relative to the second sample.
- 31. The method of claim 1 further comprising the step of selecting said transcript or translation product of the first group from the group consisting of SLC14A1-urea transporter (U35735), QYP3A1-cytochrome P-450 (P-450 HFLa) (D00408), KRT5-keratin type II (M21389), P15—protease inhibitor 5 (maspin) (U04313), ATDC—ataxia-telangiectasia group D-associated protein (L24203), TGFB3 (transforming growth factor, beta 3) (X14885), GSTM3 (glutathione transferase M3) (J05459), hKvBeta3 (potassium voltage-gated channel, beta member 3) (L39833), GPM6B (glycoprotein M6B) (U45955), SRPX (sushi-repeat-containing protein, X chromosome) (U61374), ROR2 (receptor tyrosine kinase-like orphan receptor 2) (M97639), RBP (retinol binding protein) (X00129), H19 RNA gene (M32053), PLCE (phospholipase C, epsilon) (D42108), MYH11 (myosin, heavy polypeptide II, smooth muscle) (D10667), CSTA (cystatin A (stefin A)) (D88422), NELL2 (nel (chicken)-like 2) (D83018), ID4 (inhibitor of DNA binding 4, dominant negative helix-loop-helix protein) (U28368), FGFR1 (fibroblast growth factor receptor 1) (X66945), KCNMB1 (potassium large conductance calcium-activated channel, subfamily M, beta member 1) (U25138), and CAMK2G (calcium/calmodulm-dependent protein kinase (CaM kinase) II gamma) (U50360) and selecting said transcript or translation product of the second group from the group consisting of Hepsin (X07732), PLAB/Prostate differentiation factor/TGF-β (AB000584), GJB1/gap junction protein (X04325), Neuronal apoptosis inhibitory protein (U19251), TMSNB/NB thymosin p (D82345), Human mRNA KIAA00167, partial sequence (D28589), and PLA2G7/LDL-phospholipase A2 (U24577).
- 32. The method of claim 31 further comprising the step of identifying the patient as having a poor outcome when expression of at least one of the first group of RNA transcripts or translation products is found to be at least 4.0-fold lower in the first sample relative to the second sample, and expression of at least one of the second group of RNA transcripts or translation products is found to be at least 4.0-fold higher in the first sample relative to the second sample.
- 33. The method of claim 1 wherein the neoplastic tissue comprises Gleason grade 4/5 prostate carcinoma cells.
- 34. The method of claim 1 wherein the nonmalignant human prostate tissue is benign prostate hyperplasia.
- 35. A method for evaluating carcinogenicity of an agent to human prostate cells comprising the steps of:
comparing level of expression of at least one transcript or its translation product from a first or a second group of RNA transcripts in a first sample of human prostate cells contacted with a test agent to level of expression in a second sample of human prostate cells not contacted with the test agent, wherein the first group of RNA transcripts consists of transcripts of genes selected from the group consisting of SLC14A1-urea transporter (U35735), CYP3A1-cytochrome P-450 (P-450 HFLa) (D00408), KRT5—keratin type II (M21389), P15—protease inhibitor 5 (maspin) (U04313), ATDC—ataxia-telangiectasia group D-associated protein (L24203), TGFB3 (transforming growth factor, beta 3) (X14885), GSTM3 (glutathione transferase M3) (J05459), hKvBeta3 (potassium voltage-gated channel, beta member 3) (L39833), GPM6B (glycoprotein M6B) (U45955), SRPX (sushi-repeat containing protein, X chromosome) (U61374), ROR2 (receptor tyrosine knase-like orphan receptor 2) (M97639), RBP (retinol binding protein) (X00129), H19 RNA gene (M32053), PLCE (phospholipase C, epsilon) (D42108), MYH11 (myosin, heavy polypeptide II, smooth muscle) (D10667), CSTA (cystatin A (stefin A)) (D88422), NELL2 (nel (chicken)-like 2) (D83018), ID4 (inhibitor of DNA binding 4, dominant negative helix-loop-helix protein) (U28368), FGFR1 (fibroblast growth factor receptor 1) (X66945), KCNMBI (potassium large conductance calcium-activated channel, subfamily M, beta member 1) (U25138), CAMK2G (calcium/calmodulin-dependent protein kinase (CaM knase) II gamma) (U50360), TRPC 1 (transient receptor potential channel 1) (X89066), BRF2 (butyrate response factor 2 (EGF-response factor 2)) (X78992), RARRES2 (retinoic acid receptor responder (tazarotene induced) 2) (U77594), gasl gene (L13698), SERPINF1 (serine (or cysteine) proteinase inhibitor, clade F (alpha-2 antiplasmin, pigment epithelium derived factor), member 1) (U29953), caveolin-2 (U32114), ETV5 (ets variant gene 5 (ets-related molecule)) (X96381), KIAA0003/ANGPT1 (angiopoietin 1) (D13628), MT1L (metallothionein 1 L) (X76717), KIAK0002/CCND2 (cyclin 132) (D13639), VCL (vinculin) (M33308), COX7Al (cytochrome c oxidase subunit VIIa polypeptide 1 (muscle)) (M83186), PYGL (phosphorylase, glycogen; liver (Hers disease, glycogen storage disease type VI)) (M14636), SLC2A5 (solute carrier family 2 (facilitated glucose transporter), member 5) (M55531), annexin VI (p68) (Y00097), DRAL (L42176), DPYSL3 (dihydropyrimidinaselike 3) (D78014), A-362G6.1 (hypothetical protein A-362G6.1) (U95740 ma), TIMP3 (tissue inhibitor of metalloproteinase 3) (D45917), MIG2 (mitogen inducible 2 (Z24725), SDF1 (stromal cell-derived factor 1) (U19495), KIM0025 (KIM0025 gene product; MMS-inducible gene) (D14695), PRNP (prion protein (p27-30)) (X83416), AOX1 (aldehyde oxidase 1) (L 1005), PLP2 (proteolipid protein 2 (colonic epithelium-enriched)) (L09604), MT2A (metallothionein 2A) (V00594), RRAS (related RAS viral (r-ras) oncogene homolog) (M 14949), and LIP2 (D00017), and the second group of RNA transcripts consists of transcripts of genes selected from the group consisting of Hepsin (X07732), PLAB/Prostate differentiation factor/TGF-β (AB000584), GJB1/gap junction protein (X04325), Neuronal apoptosis inhibitory protein (U19251), TMSNB/NB thymosin β (D82345), Human mRNA KIAA00167, partial sequence (D28589), PLA2G7/LDL-phospholipase A2 (U24577), Homeo box c8 protein (M16938), Human carcinoma associated antigen GA733-2 (M93036), HSD17B4/17β-hydroxysteroid dehydrogenase IV (X87176), ALCAM/Activated leucocyte cell adhesion molecule (U30999), Macmarcks (HG1612-HT1612), ERK3 (extracellular signal-regulated kinase) (X80692), RNA polymerase II subunit (hsRPB8) (U37689), NBK apoptotic inducer protein (X89986), PYCR1/Pyrroline 5-carboxylate reductase 1 (M77836), APEX nuclease (D13370), Ring zinc-forger protein (ANF127-xp) (U41315), SLC25A6/Solute carrier family 25, member A6 (J03592), and Arginine-rich protein (M83751), wherein an agent which decreases the level of expression of at least one of the genes of the first group, or an agent which increases the level of expression of at least one of the genes in the second group is a potential carcinogen to human prostate cells.
- 36. The method of claim 35 further comprising the step of comparing the level of expression of at least two of the transcripts or translation products.
- 37. The method of claim 35 further comprising the step of comparing the level of expression of at least five of the transcripts or translation products.
- 38. The method of claim 35 further comprising the step of comparing the level of expression of at least ten of the transcripts or translation products.
- 39. The method of claim 35 further comprising the step of comparing the level of expression of at least twenty of the transcripts or translation products.
- 40. The method of claim 35 further comprising the step of comparing the level of expression of at least fifty of the transcripts or translation products.
- 41. The method of claim 35 further comprising the step of comparing the level of expression of at least sixty of the transcripts or translation products.
- 42. The method of claim 35 further comprising the step of comparing the level of expression of sixty-nine of the transcripts or translation products.
- 43. The method of claim 35 further comprising the step of determining the level of expression of RNA transcripts using an array of nucleic acid molecules.
- 44. The method of claim 35 further comprising the step of comparing the level of expression of at least one transcript.
- 45. A method of slowing progression of prostate cancer in a patient comprising the step of:
administering to prostate cancer cells of the patient a polynucleotide comprising a coding sequence of a gene selected from the group consisting of SLC14A1-urea transporter (U35735), CYP3A1-cytochrome P-450 (P-450 HFLa) (D00408), KRT5-keratin type II (M21389), P15—protease inhibitor 5 (maspin) (U04313), ATDC—ataxia-telangiectasia group D-associated protein (L24203), TGFB3 (transforming growth factor, beta 3) (X14885), GSTM3 (glutathione transferase M3) (J05459), hKvBeta3 (potassium voltage-gated channel, beta member 3) (L39833), GPM6B (glycoprotein M6B) (U45955), SRPX (sushi-repeat-containing protein, X chromosome) (U61374), ROR2 (receptor tyrosine kinase-like orphan receptor 2) (M97639), RBP (retinol binding protein) (X00129), H19 RNA gene (M32053), PLCE (phospholipase C, epsilon) (D42108), MYH11 (myosin, heavy polypeptide II, smooth muscle) (D10667), CSTA (cystatin A (stefin A)) (D88422), NELL2 (nel (chicken)-like 2) (D83018), ID4 (inhibitor of DNA binding 4, dominant negative helix-loop-helix protein) (U28368), FGFR1 (fibroblast growth factor receptor 1) (X66945), KCNMB1 (potassium large conductance calcium-activated channel, subfamily M, beta member 1) (U25138), CAMK2G (calcium/calmodulm-dependent protein kmase (CaM kinase) II gamma) (U50360), TRPC1 (transient receptor potential channel 1) (X89066), BRF2 (butyrate response factor 2 (EGF-response factor 2)) (X78992), RARRES2 (retinoic acid receptor responder (tazarotene induced) 2) (U77594), gasl gene (L13698), SERPINF1 (serine (or cysteine) proteinase inhibitor, clade F (alpha-2 antiplasmin, pigment epithelium derived factor), member 1) (U29953), caveolin-2 (U32114), ETV5 (ets variant gene 5 (ets-related molecule)) (X96381), KIAA0003/ANGPT1 (angiopoietin 1) (D13628), MT1L (metallothionein 1 L) (X76717), KIAK0002/CCND2 (cyclin D2) (D13639), VCL (vinculin) (M33308), COX7A1 (cytochrome c oxidase subunit VIIa polypeptide 1 (muscle)) (M83186), PYGL (phosphorylase, glycogen; liver (Hers disease, glycogen storage disease type VI)) (M14636), SLC2A5 (solute carrier family 2 (facilitated glucose transporter), member 5) (M55531), annexin VI (p68) (Y00097), DRAL (L42176), DPYSL3 (dihydropyrimidinaselike 3) (D78014), A-362G6.1 (hypothetical protein A-362G6.1) (U95740_rna), TIMP3 (tissue inhibitor of metalloproteinase 3) (D45917), MIG2 (mitogen inducible 2 (Z24725), SDF1 (stromal cell-derived factor 1) (U19495), KIAA0025 (KIM0025 gene product; MMS-inducible gene) (D14695), PRNP (prion protein (p27-30)) (X83416), AOX1 (aldehyde oxidase 1) (L11005), PLP2 (proteolipid protein 2 (colonic epithelium-enriched)) (L09604), MT2A (metallothionein 2A) (V00594), RRAS (related RAS viral (r-ras) oncogene homolog) (M14949), and LIP2 (D00017), whereby the gene is expressed in the prostate cancer cells, thereby slowing progression of prostate cancer in the patient.
- 46. The method of claim 45 wherein said gene is maspin (U04313).
- 47. A method of slowing progression of prostate cancer in a patient, comprising the step of:
administering to prostate cancer cells of a patient an antisense construct comprising at least 12 nucleotides of a coding sequence of a gene selected from the group consisting of Hepsin (X07732), PLAB/Prostate differentiation factor/TGF-β (AB000584), GJB1/gap junction protein (X04325), Neuronal apoptosis inhibitory protein (U19251), TMSNB/NB thymosin β (D82345), Human mRNA KIAA00167, partial sequence (D28589), PLA2G7/LDL-phospholipase A2 (U24577), Homeo box c8 protein (M16938), Human carcinoma associated antigen GA733-2 (M93036), HSD17B4/17β-hydroxysteroid dehydrogenase IV (X87176), ALCAM/Activated leucocyte cell adhesion molecule (U30999), Macmarcks (HG1612-HT1612), ERK3 (extracellular signal-regulated kinase) (X80692), RNA polymerase II subunit (hsRPB8) (U37689), NBK apoptosic inducer protein (X89986), PYCR1/Pyrroline 5-carboxylate reductase 1 (M77836), APEX nuclease (D13370), Ring zinc-finger protein (ANF 127-xp) (U41315), SLC25A6/Solute carrier family 25, member A6 (J03592), and Arginine-rich protein (M83751), wherein the coding sequence is in a 3′ to 5′ orientation with respect to a promoter which controls its expression, whereby an antisense RNA is expressed in cells of the cancer, thereby slowing progression of prostate cancer in the patient.
- 48. The method of claim 47 wherein said gene is hepsin (X07732).
- 49. A method of slowing progression of prostate cancer in a patient, comprising the step of:
administering to prostate cancer cells of a patient an antibody which specifically binds to a protein expressed from a gene selected from the group consisting of Hepsin (X07732), PLAB/Prostate differentiation factor/TGF-β (AB000584), GJB1/gap junction protein (X04325), Neuronal apoptosis inhibitory protein (U19251), TMSNB/NB thymosin p (D82345), Human mRNA KIAA00167, partial sequence (D28589), PLA2G7/LDL-phospholipase A2 (U24577), Homeo box c8 protein (M16938), Human carcinoma associated antigen GA733-2 (M93036), HSD17B4/17β-hydroxysteroid dehydrogenase IV (X87176), ALCAM/Activated leucocyte cell adhesion molecule (U30999), Macmarcks (HG1612-HT1612), ERK3 (extracellular signal-regulated kinase) (X80692), RNA polymerase II subunit (hsRPB8) (U37689), NBK apoptotic inducer protein (X89986), PYCR1/Pyrroline 5-carboxylate reductase 1 (M77836), APEX nuclease (D13370), Ring zinc-finger protein (ANF127-xp) (U41315), SLC25A6/Solute carrier family 25, member A6 (J03592), and Arginine-rich protein (M83751), whereby the antibody binds to the protein, thereby slowing progression of prostate cancer in the patient.
- 50. The method of claim 49 wherein the antibody specifically binds hepsin.
- 51. A method of screening for candidate drugs useful in the treatment of prostate cancer, comprising the steps of:
contacting a prostate cancer cell with a test substance; monitoring expression of a transcript or its translation product, wherein the transcript is of a gene selected from a first or a second group wherein the first group of genes is selected from the group consisting of SLC14A1-urea transporter (U35735), CYP3A1-cytochrome P-450 (P-450 HFLa) (D00408), KRT5—keratin type II (M21389), P15—protease inhibitor 5 (maspin) (U04313), ATDC—ataxia-telangiectasia group D-associated protein (L24203), TGFB3 (transforming growth factor, beta 3) (X14885), GSTM3 (glutathione transferase M3) (J05459), hKvBeta3 (potassium voltage-gated channel, beta member 3) (L39833), GPM6B (glycoprotein M6B) (U45955), SRPX (sushi-repeat-containing protein, X chromosome) (U61374), ROR2 (receptor tyrosine kinase-like orphan receptor 2) (M97639), RBP (retinol binding protein) (X00129), H19 RNA gene (M32053), PLCE (phospholipase C, epsilon) (D42108), MYH11 (myosin, heavy polypeptide II, smooth muscle) (D10667), CSTA (cystatin A (stefin A)) (D88422), NELL2 (nel (chicken)-like 2) (D83018), ID4 (inhibitor of DNA binding 4, dominant negative helix-loop-helix protein) (U28368), FGFR1 (fibroblast growth factor receptor 1) (X66945), KCNMB1 (potassium large conductance calcium-activated channel, subfamily M, beta member 1) (U25138), CAMK2G (calcium/calmodulin-dependent protein kinase (CaM kinase) II gamma) (U50360), TRPC1 (transient receptor potential channel 1) (X89066), BRF2 (butyrate response factor 2 (EGF-response factor 2)) (X78992), RARRES2 (retinoic acid receptor responder (tazarotene induced) 2) (U77594), gas1 gene (L13698), SERPINF1 (serine (or cysteine) proteinase inhibitor, clade F (alpha-2 antiplasmin, pigment epithelium derived factor), member 1) (U29953), caveolin-2 (U32114), ETV5 (ets variant gene 5 (ets-related molecule)) (X96381), KIAA0003/ANGPT1 (angiopoietin 1) (D13628), MT1L (metallothionein 1L) (X76717), KIAK0002/CCND2 (cyclin D2) (D13639), VCL (vinculin) (M33308), COX7A1 (cytochrome c oxidase subumt VIIa polypeptide 1 (muscle)) (M83186), PYGL (phosphorylase, glycogen; liver (Hers disease, glycogen storage disease type VI)) (M14636), SLC2A5 (solute carrier family 2 (facilitated glucose transporter), member 5) (M55531), annexin VI (p68) (Y00097), DRAL (L42176), DPYSL3 (dihydropyrimidinase-like 3) (D78014), A-362G6.1 (hypothetical protein A-362G6.1) (U95740 ma), TIMP3 (tissue inhibitor of metalloproteinase 3) (D45917), MIG2 (mitogen inducible 2 (Z24725), SDF1 (stromal cell-derived factor 1) (U19495), KIAA0025 (KIAA0025 gene product; MMS-inducible gene) (D14695), PRNP (prion protein (p27-30)) (X83416), AOX1 (aldehyde oxidase 1) (L11005), PLP2 (proteolipid protein 2 (colonic epithelium-enriched)) (L09604), MT2A (metallothionein 2A) (V00594), RRAS (related RAS viral (r-ras) oncogene homolog) (M14949), and LIP2 (D00017), and the second group is selected from the group consisting of Hepsin (X07732), PLAB/Prostate differentiation factor/TGF-β (AB000584), GJB1/gap junction protein (X04325), Neuronal apoptosis inhibitory protein (U19251), TMSNB/NB thymosin p (D82345), Human mRNA KIAA00167, partial sequence (D28589), PLA2G7/LDL-phospholipase A2 (U24577), Homeo box c8 protein (M16938), Human carcinoma associated antigen GA733-2 (M93036), HSD17B4/17β-hydroxysteroid dehydrogenase IV (X87176), ALCAM/Activated leucocyte cell adhesion molecule (U30999), Macmarcks (HG1612-HT1612), ERK3 (extracellular signal-regulated kinase) (X80692), RNA polymerase II subunit (hsRPB8) (U37689), NBK apoptosic inducer protein (X89986), PYCR1/Pyrroline 5-carboxylate reductase 1 (M77836), APEX nuclease (D13370), Ring zinc-finger protein (ANF127-xp) (U41315), SLC25A6/Solute carrier family 25, member A6 (J03592), and Arginine-rich protein (M83751); and identifying a test substance as a candidate drug useful for treating prostate cancer if it increases expression of at least one of the genes in the first group or decreases expression of at least one of the genes in the second group.
- 52. The method of claim 51 further comprising the step of identifying the test substance as a candidate drug if it increases expression of at least two of the genes selected from the first group or decreases expression of at least two of the genes selected from the second group.
- 53. The method of claim 51 further comprising the step of identifying the test substance as a candidate drug if it increases expression of at least five of the genes selected from the first group or decreases expression of at least five of the genes selected from the second group.
- 54. The method of claim 51 further comprising the step of identifying the test substance as a candidate drug if it increases expression of at least ten of the genes selected from the first group or decreases expression of at least ten of the genes from the second group.
- 55. The method of claim 51 further comprising the step of identifying the test substance as a candidate drug if it increases expression of at least twenty of the genes selected from the first group or decreases expression of at least twenty of the genes selected from the second group.
- 56. The method of claim 51 further comprising the step of determining the level of expression of RNA transcripts using an array of nucleic acid molecules.
- 57. The method of claim 51 further comprising the step of monitoring expression of at least one transcript.
- 58. A method for diagnosing prostate cancer in a patient, comprising the steps of:
comparing level of expression of at least one RNA transcript or its translation product in a test sample of prostate tissue to level of expression of the at least one transcript or translation product in a control sample of prostate tissue, wherein the test sample of prostate tissue is suspected of being neoplastic and the control sample is nonmalignant prostate tissue, wherein the at least one RNA transcript or its translation product is selected from a first or a second group of RNA transcripts or translation products, wherein the first group of RNA transcripts consists of transcripts of genes selected from the group consisting of SLC14A1-urea transporter (U35735), CYP3A1-cytochrome P-450 (P-450 HFLa) (D00408), KRT5—keratin type II (M21389), P15—protease inhibitor 5 (maspin) (U04313), ATDC—ataxia-telangiectasia group D-associated protein (L24203), TGFB3 (transforming growth factor, beta 3) (X14885), GSTM3 (glutathione transferase M3) (J05459), hKvBeta3 (potassium voltage-gated channel, beta member 3) (L39833), GPM6B (glycoprotein M6B) (U45955), SRPX (sushi-repeat-containing protein, X chromosome) (U61374), ROR2 (receptor tyrosine kinase-like orphan receptor 2) (M97639), RBP (retinol binding protein) (X00129), H19 RNA gene (M32053), PLCE (phospholipase C, epsilon) (D42108), MYH11 (myosin, heavy polypeptide II, smooth muscle) (D10667), CSTA (cystatin A (stefin A)) (D88422), NELL2 (nel (chicken)-like 2) (D83018), ID4 (inhibitor of DNA binding 4, dominant negative helix-loop-helix protein) (U28368), FGFR1 (fibroblast growth factor receptor 1) (X66945), KCNMB 1 (potassium large conductance calcium-activated channel, subfamily M, beta member 1) (U25138), CAMK2G (calcium/calmodulin-dependent protein kinase (CaM kinase) II gamma) (U50360), TRPC1 (transient receptor potential channel 1) (X89066), BRF2 (butyrate response factor 2 (EGF-response factor 2)) (X78992), RARRES2 (retinoic acid receptor responder (tazarotene induced) 2) (U77594), gas1 gene (L13698), SERPINF1 (serine (or cysteine) proteinase inhibitor, clade F (alpha-2 antiplasmin, pigment epithelium derived factor), member 1) (U29953), caveolin-2 (U32114), ETV5 (ets variant gene 5 (ets-related molecule)) (X96381), KIAA0003/ANGPT1 (angiopoietin 1) (D13628), MT1L (metallothionein 1L) (X76717), KIAK0002/CCND2 (cyclin D2) (D13639), VCL (vinculin) (M33308), COX7Al (cytochrome c oxidase subunit VIIa polypeptide 1 (muscle)) (M83186), PYGL (phosphorylase, glycogen; liver (Hers disease, glycogen storage disease type VI)) (M14636), SLC2A5 (solute carrier family 2 (facilitated glucose transporter), member 5) (M55531), annexin VI (p68) (Y00097), DRAL (L42176), DPYSL3 (dihydropyrimidinase-like 3) (D78014), A-362G6.1 (hypothetical protein A-362G6.1) (U95740_rna), TIMP3 (tissue inhibitor of metalloproteinase 3) (D45917), MIG2 (mitogen inducible 2 (Z24725), SDF1 (stromal cell-derived factor 1) (U19495), KIAA0025 (KIM0025 gene product; MMS-inducible gene) (D14695), PRNP (prion protein (p27-30)) (X83416), AOX1 (aldehyde oxidase 1) (LI 1005), PLP2 (proteolipid protein 2 (colonic epithelium-enriched)) (L09604), MT2A (metallothionein 2A) (V00594), RRAS (related RAS viral (r-ras) oncogene homolog) (M14949), and LIP2 (D00017), and wherein the second group of RNA transcripts consists of transcripts of genes selected from the group consisting of Hepsin (X07732), PLAB/Prostate differentiation factor/TGF-β (AB000584), GJB1/gap junction protein (X04325), Neuronal apoptosis inhibitory protein (U19251), TMSNB/NB thymosin β (D82345), Human mRNA KIAA00167, partial sequence (D28589), PLA2G7/LDL-phospholipase A2 (U24577), Homeo box c8 protein (M16938), Human carcinoma associated antigen GA733-2 (M93036), HSD17B4/17β-hydroxysteroid dehydrogenase IV (X87176), ALCAM/Activated leucocyte cell adhesion molecule (U30999), Macmarcks (HG1612-HT1612), ERK3 (extracellular signal-regulated kinase) (X80692), RNA polymerase II subunit (hsRPB8) (U37689), NBK apoptosic inducer protein (X89986), PYCR1/Pyrroline 5-carboxylate reductase 1 (M77836), APEX nuclease (D13370), Ring zinc-finger protein (ANF127-xp) (U41315), SLC25A6/Solute carrier family 25, member A6 (J03592), and Arginine-rich protein (M83751); and identifying the test sample as cancerous when expression of at least one of the first group of RNA transcripts or translation products is found to be lower in the test sample than in the control sample, and expression of at least one of the second group of transcripts or translation products is found to be higher in the test sample than in the control sample.
- 59. The method of claim 58 further comprising the step of determining the level of expression of RNA transcripts using an array of nucleic acid molecules.
- 60. The method of claim 58 further comprising the step of comparing the level of expression of at least one RNA transcript in the test sample to the level of expression of said transcript in the control sample.
- 61. The method of claim 58 further comprising the step of comparing transcripts or translation products of at least two of the genes of the first group.
- 62. The method of claim 58 further comprising the step of comparing transcripts or translation products of at least two of the genes of the second group.
- 63. The method of claim 58 further comprising the step of comparing transcripts or translation products of at least five of the genes of the first group.
- 64. The method of claim 58 further comprising the step of comparing transcripts or translation products of at least five of the genes of the second group.
- 65. The method of claim 58 further comprising the step of comparing transcripts or translation products of at least ten of the genes of the first group.
- 66. The method of claim 58 further comprising the step of comparing transcripts or translation products of at least ten of the genes of the second group.
- 67. The method of claim 58 further comprising the step of comparing transcripts or translation products of at least twenty of the genes of the first group.
- 68. The method of claim 58 further comprising the step of comparing transcripts or translation products of at least twenty of the genes of the second group.
- 69. The method of claim 58 further comprising the step of comparing transcripts or translation products of at least thirty of the genes of the first group.
- 70. The method of claim 58 further comprising the step of comparing transcripts or translation products of at least forty-nine of the genes of the first group.
- 71. The method of claim 58 further comprising the step of determining the expression level of maspin (U04313) transcript or its translation product.
- 72. The method of claim 58 further comprising the step of determining the expression level of hepsin (X07732) transcript or its translation product.
- 73. The method of claim 58 further comprising the step of comparing transcripts or translation products of at least two of the genes in each group of RNA transcripts or translation products.
- 74. The method of claim 58 further comprising the step of comparing transcripts or translation products of at least five of the genes in each group of transcripts or translation products.
- 75. The method of claim 58 further comprising the step of comparing transcripts or translation products of at least ten of the genes in each group of transcripts or translation products.
- 76. The method of claim 58 further comprising the step of comparing transcripts or translation products of at least twenty of the genes in each group of transcripts or translation products.
- 77. The method of claim 58 further comprising the step of comparing at least thirty of the transcripts or translation products in the fast group and twenty of the transcripts or translation products in the second group.
- 78. The method of claim 58 further comprising the step of comparing at least forty of the transcripts or translation products in the first group and twenty of the transcripts or translation products in the second group.
- 79. The method of claim 58 further comprising the step of comparing at least forty-nine of the transcripts or translation products in the first group and twenty of the transcripts or translation products in the second group.
- 80. The method of claim 58 wherein the at least one RNA transcript or its translation product of the first group of RNA transcripts or translation products comprises the transcript of the gene maspin (U04313).
- 81. The method of claim 58 wherein the at least one RNA transcript or its translation product of the second group of RNA transcripts comprises the transcript of the gene hepsin (X07732).
- 82. The method of claim 58 wherein the test sample comprises Gleason grade 4/5 prostate carcinoma cells.
- 83. The method of claim 58 wherein the nonmalignant prostate tissue is benign prostate hyperplasia tissue.
- 84. The method of claim 58 further comprising the step of identifying the test sample as Gleason grade 4/5 prostate carcinoma.
- 85. An array of nucleic acid molecules in which the nucleic acid molecules comprise a set of members having distinct sequences, wherein each member is fixed at a distinct location on the array, wherein at least 10% of the members on the array comprise at least 15 contiguous nucleotides of genes selected from the group consisting of SLC14A1-urea transporter (U35735), CYP3A1-cytochrome P-450 (P-450 HFLa) (D00408), KRT5—keratin type II (M21389), P15—protease inhibitor 5 (maspin) (U04313), ATDC—ataxia-telangiectasia group D-associated protein (L24203), TGFB3 (transforming growth factor, beta 3) (X14885), GSTM3 (glutathione; transferase M3) (J05459), hKvBeta3 (potassium voltage-gated channel, beta member 3) (L39833), GPM6B (glycoprotein M6B) (U45955), SRPX (sushi-repeatcontaining protein, X chromosome) (U61374), ROR2 (receptor tyrosine kinase-like orphan receptor 2) (M97639), RBP (retinol binding protein) (X00129), H19 RNA gene (M32053), PLCE (phospholipase C, epsilon) (D42108), MYH11 (myosin, heavy polypeptide II, smooth muscle) (D10667), CSTA (cystatin A (stein A)) (D88422), NELL2 (nel (chicken)-like 2) (D83018), ID4 (inhibitor of DNA binding 4, dominant negative helix-loop-helix protein) (U28368), FGFR1 (fibroblast growth factor receptor 1) (X66945), KCNMB1 (potassium large conductance calcium-activated channel, subfamily M, beta member 1) (U25138), CAMK2G (calcium/calmodulin-dependent protein kinase (CaM kinase) II gamma) (U50360), TRPC1 (transient receptor potential channel 1) (X89066), BRF2 (butyrate response factor 2 (EGF-response factor 2)) (X78992), RARRES2 (retinoic acid receptor responder (tazarotene induced) 2) (U77594), gas1 gene (L13698), SERPINF1 (serine (or cysteme) proteinase inhibitor, clade F (alpha-2 antiplasmin, pigment epithelium derived factor), member 1) (U29953), caveolin-2 (U32114), ETV5 (ets variant gene 5 (ets-related molecule)) (X96381), KIAA0003/ANGPT1 (angiopoietin 1) (D13628), MT1L (metallothionein 1L) (X76717), KIAK0002/CCND2 (cyclin D2) (D13639), VCL (vinculin) (M33308), COX7A1 (cytochrome c oxidase subunit VIIa polypeptide 1 (muscle)) (M83186), PYGL (phosphorylase, glycogen; liver (Hers disease, glycogen storage disease type VI)) (M14636), SLC2A5 (solute carrier family 2 (facilitated glucose transporter), member 5) (M55531), annexin VI (p68) (Y00097), DRAL (L42176), DPYSL3 (dihydropyrimidinaselike 3) (D78014), A-362G6.1 (hypothetical protein A-362G6.1) (U95740_rna), TIMP3 (tissue inhibitor of metalloproteinase 3) (D45917), MIG2 (mitogen inducible 2 (Z24725), SDF1 (stromal cell-derived factor 1) (U19495), KIM0025 (KIM0025 gene product; MMS-inducible gene) (D14695), PRNP (prion protein (p27-30)) (X83416), AOX1 (aldehyde oxidase 1) (L11005), PLP2 (proteolipid protein 2 (colonic epithelium-enriched)) (L09604), MT2A (metallothionem 2A) (V00594), RRAS (related RAS viral (r-ras) oncogene homolog) (M14949), LIP2 (D00017), Hepsin (X07732), PLAB/Prostate differentiation factor/TGF-β (AB000584), GJBI/gap junction protein (X04325), Neuronal apoptosis inhibitory protein (U19251), TMSNB/NB thymosin β (D82345), Human mRNA KIAA00167, partial sequence (D28589), PLA2G7/LDL-phospholipase A2 (U24577), Homeo box c8 protein (M16938), Human carcinoma associated antigen GA733-2 (M93036), HSD17B4/17β-hydroxysteroid dehydrogenase IV (X87176), ALCAM/Activated leucocyte cell adhesion molecule (U30999), Macmarcks (HG1612-HT1612), ERK3 (extracellular signal-regulated kmase) (X80692), RNA polymerase II subunit (hsRPB8) (U37689), NBK apoptosic inducer protein (X89986), PYCR1/Pyrroline 5-carboxylate reductase I (M77836), APEX nuclease (D13370), Ring zinc-finger protein (ANF127-xp) (U41315), SLC25A6/Solute carrier family 25, member A6 (J03592), and Arginine-rich protein (M83751).
- 86. The array of claim 85 wherein at least 20% of the members are selected from the group.
- 87. The array of claim 85 wherein at least 30% of the members are selected from the group.
- 88. The array of claim 85 wherein at least 40% of the members are selected from the group.
- 89. The array of claim 85 wherein at least 50% of the members are selected from the group.
- 90. A method for monitoring prostate cancer in a patient, comprising:
measuring level of at least one serum marker in a serum sample of a patient having prostate cancer, wherein the serum marker is a protein expressed from a first or second group of genes, wherein the first group of genes consists of P15-protease inhibitor 5 (mapsin) (U04313), TGFB3 (transforming growth factor, beta 3) (X14885), IGFBP6 (insulinlike growth factor binding protein 6) (M62402), NELL2 (nel (chicken)-like 2) (D83018), nerve growth factor (HBNF-1) (M57399), insulin-like growth factor 2 (HG3543-HT3739), SERPINF1 (serine (or cysteine) proteinase inhibitor, clade F (alpha-2 antiplasmin, pigment epithelium derived factor), member 1) (U29953), KIAA0003/ANGPT1 (angiopoietin 1) (D13628), FGF7 (fibroblast growth factor 7), TIMP (tissue inhibitor of metalloproteinase 3) (D45917), and SDF1 (stromal cell-derived factor 1) (U19495) and the second group of genes consists of the gene PLA2G7/LDL-phospholipase A2 (U24577).
- 91. The method of claim 90 further comprising the step of identifying the patient as having a poor outcome when level of the serum marker from the first group is found to be reduced in the patient relative to serum of an individual with a nonmalignant prostate or when level of the serum marker of the second group is found to be increased in the patient relative to serum of an individual with a nonmalignant prostate.
- 92. The method of claim 90 wherein the at least one serum marker measured is a protein expressed from a gene selected from the group consisting of P15-protease inhibitor 5 (mapsin) (U04313), TGFB3 (transforming growth factor, beta 3) (X14885), IGFBP6 (insulinlike growth factor binding protein 6) (M62402), NELL2 (nel (chicken)-like 2) (D83018), nerve growth factor (HBNF-1) (M57399), and insulin-like growth factor 2 (HG3543HT3739).
- 93. The method of claim 90 wherein the prostate cancer comprises Gleason grade 4/5 prostate carcinoma cells.
- 94. The method of claim 91 wherein the nonmalignant prostate comprises benign prostate hyperplasia.
- 95. The method of claim 90 further comprising the step of measuring the level of expression of at the least one serum marker by an antibody.
- 96. A method of diagnosing prostate cancer in a patient comprising:
measuring level of at least one serum marker in serum of a patient suspected of having prostate cancer, wherein the serum marker is a protein expressed from a first or second group of genes, wherein the first group of genes is selected from the group consisting of P15-protease inhibitor 5 (mapsin) (U04313), TGFB3 (transforming growth factor, beta 3) (X14885), IGFBP6 (insulin-like growth factor binding protein 6) (M62402), NELL2 (nel (chicken)-like 2) (D83018), nerve growth factor (HBNF-1) (M57399), insulin-like growth factor 2 (HG3543-HT3739), SERPINF1 (serine (or cysteme) proteinase inhibitor, clade F (alpha-2 antiplasmin, pigment epithelium derived factor), member 1) (U29953), KIAA0003/ANGPT 1 (angiopoietin 1) (D13628), FGF7 (fibroblast growth factor 7), TIMP (tissue inhibitor of metalloproteinase 3) (D45917), and SDF1 (stromal cell-derived factor 1) (U19495), and the second group of genes consists of the gene PLA2G7/LDL-phospholipase A2 (U24577); identifying the patient as having prostate carcinoma when level of the serum marker from the first group is found to be reduced in the serum of the patient relative to an individual with a nonmalignant prostate or level of the serum marker from the second group is found to be increased in the serum of the patient relative to an individual with a nonmalignant prostate.
- 97. The method of claim 96 wherein the serum marker measured is a protein expressed from a gene of the first group selected from the group consisting of P15-protease inhibitor 5 (mapsin) (U04313), TGFB3 (transforming growth factor, beta 3) (X14885), IGFBP6 (insulinlike growth factor binding protein 6) (M62402), NELL2 (nel(chicken)-like 2) (D83018), nerve growth factor (HBNF-1) (M57399), and insulin-like growth factor 2 (HG3543-HT3739).
- 98. The method of claim 96 further comprising the step of identifying the prostate cancer as Gleason grade 4/5 prostate carcinoma.
- 99. The method of claim 96 wherein the nonmalignant prostate comprises benign prostate hyperplasia.
- 100. The method of claim 96 further comprising the step of measuring the level of expression of at the least one serum marker by an antibody.
RELATED APPLICATIONS
[0001] This application claims priority to Provisional Application Serial No. 60/312,745 filed Aug. 17, 2001, which is herein incorporated by reference in its entirety for all purposes.
Provisional Applications (1)
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Number |
Date |
Country |
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60312745 |
Aug 2001 |
US |