Gleason grade 4/5 prostate cancer genes

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.

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.

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.

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.

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).

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.