Molecular genetic profiling of gleason grades 3 and 4/5 prostate cancer

• US 20040029151A1
• Filed: 04/09/2003
• Published: 02/12/2004
• Est. Priority Date: 04/09/2002
• Status: Abandoned Application

• Current Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.), Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Stamey, Thomas A., Chen, Zuxiong, Palma, John F., Warrington, Janet A., Mahadevappa, Mamatha, Zhang, Zhaomei, Fan, Zhenbin, McNeal, John E., Nolley, Rosalie, Caldwell, Mitchell C.
• Application Number:
  US10/411,537
• Publication Number:
  US 20040029151A1
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/112 Disease subtyping, staging or classification
• CPC Class Codes: C12Q 2600/136 Screening for pharmacological compounds

Abstract

Many genes are affected in prostate cancers which have not been previously identified. This includes genes that have been up-regulated or down-regulated. Monitoring the expression levels of these genes is useful to identify the existence of prostate cancer. Also, monitoring the expression levels of these genes is useful to predict the effectiveness of treatment, outcome, use of therapeutics, and screening drugs useful for the treatment of prostate cancer.

Claims

1. 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 GST alpha glutathione S-transferase exon 2 (X65727), Glutathione S-transferase Ha subunit 2 (GST) (M16594), transglutaminase (HG4020-HT4290), P15-protease inhibitor 5 (maspin) (U04313), L Arg;

Gly amidinotransferase (S68805), KIAA0089 (D42047), RTVP-1 protein (X91911), GSTP1 (glutathione S-transferase pi) (M24485), L-arginine;

glycine amidinotransferase (X86401), DNA endothelin-A receptor (D11151), Id1 (HG3342-HT3519), bcl-2 (M14745), Protein Phosphatase Inhibitor Homolog (HG3570-HG3773), pS2 protein (X52003), hAOX (aldehyde oxidase) (L11005), glutaredoxin (X76648), CO-029 (M35252), NADP dependent leukotriene b4 12-hydroxydehydrogenase (D49387), Glucocorticoid receptor alpha (M10901), Glucocorticoid receptor beta (HG4582-HT4987), ZAKI-4 from skin fibroblast (D83407), syndecan (exon 2-5) (Z48199), S-adenosylmethionine decarboxylase (M21154), hevin-like protein (X86693), gas 1 (L13698), pcHDP7 liver dipeptidyl peptidase IV (X60708), adult male liver squalene epoxidase (D78129), cathepsin H (X16832), oestrogen receptor (X03635), Id-related helix-loop-helix protein Id4 (U28368), apM2 GS2374 (D45370), macrophage capping protein (M94345), nucleotide binding protein (L04510), DNA cystatin A (D88422), Decorin (HG3431-HT3616), RACH1 (U35735), TIG2 (tazarotene-induced

     2) (U77594), gravin (U81607), H19 RNA (M32053), adipsin/complement factor D (M84526), chondoitin sulfate proteoglycan versican V0splice-variant precursor peptide (U16306), nel-related protein 2 (D83018), IGFBP6 (insulin-like growth factor I) (X57025), cellular retinol-binding protein (M11433), laminin B1 chain (M61916), DNA primase (subunit

     58) (X74331), complement protein component C7 (J03507), neuronal membrane glycoprotein M6b (U45955), TGF-beta3 (transming growth factor-beta3) (X14885), keratonocyte growth factor (M60828), SPARC/osteonectin (J03040), K+ channel beta subunit (L39833), procollagen C-proteinase enhancer protein (PCOLCE) (L33799), GTPase homolog HeLA cell line 833 nt (S82240), alpha-2 macroglobulin (M11313), thrombospondin (X14787), CAPL protein (M80563), prepro-alpha2(I) collagen (Z74616), pigment epithelium-derived factor (U29953), aspartoacylase kidney 1435 nt (S67156), class I alcohol dehydrogenase (ADH1) alpha subunit (M12963), CRBP (retinol binding protein) (X07438), Ovarian cancer down-regulated myosin heavy chain homolog (Doc1) (U53445), Insulin-like Growth factor 2 (HG3543-HT3739), Prostaglandin D2 synthase (M98539), hIRH (intecrin-alpha) (U19495), G9i) protein alpha-subunit (X04828), tryptase-III 3′

-end (M33403), lumican (U21128), TIMP-3;

C-terminus region (D45917), 3′

UTR of unknown protein (Y09836), novel protein with short consensus repeats of six cysteines (U61374), h-SmLIM (smooth muscle LIM protein) (U46006), LACI (lipoprotein-associated coagulation inhibitor) (M59499), phospholamban (M63603), transcriptional activator hSNF2a (D26155), smooth muscle myosin heavy chain (D10667), erm exon2,3,4,5 (X96381), telomeric repeat binding factor (TRF1), N2A3 (U97105), GBP-2 (guanylate binding protein isom I) (M55542), metalloproteinase inhibitor (M32304), matrilin-2 precursor, 11-HSD11 (beta-hydroxysteroid dehydrogenase) (M76665), CCK (cholecystokinin) (L00354), apM2 GS2374 (D42047), CYP1B1 (dioxin-inducible cytochrome P450) (U03688), lung amiloride sensitive Na+ channel protein (X76180), PCP4 (PEP19) (U52969), NAT1 (anylamine N-acetyltransferase) (X17059), squalene synthase (X69141), Id-2 (helix-loop-helix protein) (M97796), Zn-alpha2-glycoprotein (X59766), Striated muscle contraction regulatory protein (Id2B) (M96843), Glucocorticoid receptor Beta (HG4582-HT4087), HLH 12R1 helix-loop-helix protein (X69111), PSE-binding factor PTF gamma subunit (U44754), cancellous bone osteoblast GS3955 (D87119), prostatic secretory protein 57 (U22178), K-sa, (Fibroblast Growth Factor Receptor) (M87770), creatine kinase-B (M16364), ornithine aminotrasnferase (M29927), epsilon-BP (IgE-binding protein) (M57710), ARL3 (GTP binding protein) (U07151), RNase 4 (D37921), MSP (Beta-microsemiprotein) (M34376), phospholipase C (D42108), lipocortin II (D00017), DBI (diazepam binding inhibitor) (M14200), KIAA0367 (AB002365), MAT8 protein (X93036), protein-tyrosin phosphatase (HU-PP-1) (U14603), imogen38 (Z68747), Cystatin A (D88422), Cytokeratine 15 (X07696), P-450 HFLa (Fetal liver cytochrome P450) (D00408), Fetal brain (239FB) mRNA from the WAGR region (U57911), Caveolin (Z18951), MLCK (myosin light chain kinase) (U48959), cardiac gap junction protein (X52947), lactate dehydrogenase B (Ec 1.1.1.27) (X13794), KIA0003 (D13628), TRPC1 protein (X89066), unknown protein (D28124), K+ channel beta subunit (L39833), COX7A (cytochrome c oxidase subunit VIIa muscle isoforms (M83186), desmin (M63391), HBNF-1 (nerve growth factor) (M57399), hIRH intercrien-alpha (U19495), fibroblast muscle-type tropomyosin (M12125), SLIM1 (skeletal muscle LIM-protein) (U60115), Adipsin/complement factor D (M84526), Epidermalkeratin-50 kDa type Ie (J00124), H-19 RNA (M32053), Keratin type II 58 kD (M21389), neuronal membrane glycoprotein M6B (U45955), GS TM3 (Glutathione transferase M3) (J05459), unknown protein (U61374), Insulin-like growth factor-2 (IG3543-HT373), IGFBP6 (insulin-like growth factor binding protein

     6) (M62402), P-cadherin (X63629), alpha-B crystalline (S45630), MaxiK potassium channel beta (U25138), MLC-2 (myosin light chain) (J02854), caveolin 2 (U32114), SOD3 (extracellular superoxide dismutase) (J02947), ERM (X96381), GLUT5 (Glucose transport-like

     5) (M55531), pigment epithelium derived factor (U29953), CRBP (retinol binding protein) (X07438), calcyclin (IG2788-HT289), dehydropyrimidinase related protein-3 (D78014), NECDIN related protein (U35139), CAPL protein (M80563), Mig-2 (Z24725), Heat shock protein 28 kDa (Z23090), smooth muscle gamma-actin (D00654), p68 (Y00097), KIAK002 (D13639), G9i) protein-alpha subunit (adelynate cyclase inhibiting GTP-b) (X04828), BPAG1 (Bullous pemphigoid antigen) (M69225), retinol-binding protein (M11433), TGF beta (transming growth factor-beta type III receptor) ((L07594), aspartoacylase (S67156), ERF-2 (X78992), complement protein component C7 (J03507), Mac-2 binding protein (L13210), vinculin (M33308), phospholamban (M63603), tissue inhibitor of metalloproteinase 3 (U14394), calponin ((D17408), glypican (hepara sulfate proteoglycan (X54232), keratinocyte growth factor (M60828), trophinin (U04811), TRPM-2 protein (M63379), filamin ABP-280 (actin binding protein) ((X53416), collagen VI alpha 2C-terminal globular domain (X15882), GBP-2 (guanylate binding protein II) (M55543), CALLA (common acute lymphoblastic leukemia antigen) (J03779), enigma ((L35240), MT-11 (X76717), ALDHI (RNA mitochondrial aldehyde dehydrogenase) (X05409), breat tumor antigen (U24576), non-muscle alpha-actinin (M95178), pur (pur-alpha) (M96684), N2A3 (U97105), 64 kD autoantigen expressed in thyroid and extra-occular muscle (X54162), GTPase homolog (S82240), arginase type II (U82256), tryptase-III (M33493), CD38 (D84276), muscarinic acetylcholine receptor (M35128), NF-H exon 1 (X15306), tenascin-C 7560 bp (X78565), LPP (IIM protein) (U49957), KIA0172 (D79994), MTIG (clone 14 VS metallothionein-IG) (J03910), smoothelin (Z49989), KIP 2 (Cdk-inhibitor p57 KIP1 (U22398), n-chimaerin (X51408), metallothionein from cadmium-treated cells (V00594), collagen VI alpha-IC-terminal globular domain (X15880), soluble carrier family 39 (zinc transporter) (NM_—

014579.1), secretoglobin family IA member I (uteroglobin) (NM_—

003357.1), serine or cystrein proteinase inhibitor (NM_—

002639.1), SIAT7E (NM_—

030965), nebulin (NM_—

004543.2), proenkephalin (NM_—

006211.1), aminolevulinate delta dehydratase (BC000977.1), hypothetical protein FIJ20513 (NM_—

017855.1), erythrocyte membrane protein band 4.1-like 3 (AI770004), adipose specific 2, unknown protein (BG109855), syndecan 1 (Z48199), keratin 5 (NM_—

000424.1), cytochrome p450 subfamily 1 (NM_—

000104.2), glutathione S-transferase pi (NM_—

000852.2), phosphorylase glycogen (NM_—

002863.1), zinc finger protein 185 (LIM domain) (NM_—

007150.1), single carrier family 16 AA705628), aminoethyltransferase (NM_—

000481), transmembrane 7 superfamily member 2 (AF096304.1), chemokine (C-X-C motif) ligand 13 (NM_—

006419.1), NEL-like 2 (NM_—

006159.1), D component of complement (adipsin) (NM_—

001928.1), EGF-containing fibulin-like EMP-1 (AI826799), retinol binding protein 1 (NM_—

002899.2), fibulin 1 (Z95331), tissue inhibitor of metalloproteinase 3 (NM_—

000362.2), signal transduction protein (NM_—

005864.1), dihydrpyramidinase-like 3 (NM_—

001387.1), WNT inhibitory factor 1 (NM_—

007191.1), signal transduction protein (SH3 containing)(NM_—

005864.1), collagen type IV alpha 6 (AI889941), suppression of tumorigenicity 5 (NM_—

005418.1),

and wherein the second group of RNA transcripts or translation products are being selected from the group consisting of pyrroline 5-carboxylase reductase (M77836), KIAA0230 (D86983), transcription factor ETR101 (M62831), TGF-beta superfamily (AB000584), intestinal trefoil factor (L08044), aldehyde dehydrogenase 6 (U07919), carcinoma associated antigen GA733-2 (M93036), IQGAP2 (RasGAP-related protein) (U51903), Macmarcks (HG1612-HT1612), KIAA0056 (D29954), SOX-4 protein (X70683), hR-PTPu protein tyrosine phosphatase (X58288), EGR2 (early growth response

     2) (J04076), DNApolymerase gamma (U60325), cystathionine beta synthase, alt splice 3 (HG2383-HT4824), CPBP (DNA-binding protein CPBP) (U44975), skeletal muscle C-protein (X66276), HU-K5 (lysophospholipase homolog) (U67963), fibromodulin (U05291), prostatin (L41351), apolipoprotein E (M12529), hEGR1 (early growth response

     1) (X52541), DNA polymerase beta (D29013), GOS3 (L49169), ANK-3 (Ankyrin G) (U13616), Gap junction protein (X04325), Hepsin (X07732), CYP1B1 (dioxin-inducible cytochrome P450 (U03688), T-cell receptor Ti rearranged gamma chain V-J-C (M30894), KIAA00167 (D28589), omithine decarboxylase (M33764), Tob (D38305), 17-beta-hydroxysteroid dehydrogenase (X87176), homeo box c8 protein (M16938), TRAIL (TNF-related apoptosis inducing ligand (U37518), cellular onco-fos (V01512), ESE-1 (epithelial-specific transcription factor) (U73843), prostate-specific membrane antigen, alternatively spliced (S76978), prostate-specific membrane antigen (M99487), T-cell receptor Ti rearranged gamma chain V-J-C region (M30894), OSF-2os (Osteoblast specific factor

     2) (D13666), LDL phospholipase A2 (U24577), MAOA (monoamine oxidase A) (M68840), ALCAM (CD6 ligand) (L38608), UDP-GalNAC;

polypeptide N-acetylgalactosaminyl transferase (X92689), NB thymosin beta (D82345), FBPI (Fructose-1,6 biphosphatase), NMB (X76534), cytochrome c-1 (J04444), ionizing radiation conferring protein (U18321), Myoglobin exon 1 (X00371), Memc (U30999), Clone 23587 sequence (U90914), pyrroline 5-carboxylate synthetase (X94453), ADE2H1 (X53793), (SNX) sorting nexin 1 (U53225), IMPDH2 (inosine monophospate dehydrogenase type II) (L33842), transcription factor E2F-5 (U31556), propionyl CoA carboxylase beta subunit (S67325), 6-pyruvoyl-tetrahydropterin synthase (D17400), ADP/ATP carrier protein (J02683), nucleoside diphosphate kinase Nm23-H2s (HG1153-HT1153), ornithine decarboxylase (M33764), CLCN3 (X78520), c-fos (V01512), PCC (propionyl-CoA carboxylase bea-subunit) (M31169), adenylsuccinate lyase (X65867), Cctg chaperonine (X74801), SIM2 (U80456), liver gap-junction protein (X04325), C-myc (L00058), HLA-DMB (U15085), carcinoma-associated antigen GA733-2 (M93036), homeo box c8 protein (M16938), GST-1 Hs GTP binding protein (X17219), Brain guanine nucleotide binding protein (M17219), spermidine synthase (M34338), NAD-dependent methylene tetrahydrofolate dehydrogenase cyclohydrolase (E.C. 1.5.1.15) (X16396), C8FW phosphoprotein (AJ000480), NBK apoptotic inducer protein (X89986), TK (t-ansketolase) (L12711), MNK1 (AB000409), fatty acid synthase (S80437), tubulin beta (HG4322-HT4592), testican (X73608), Arg protein kinasebinding protein (X95632), DNA polymerase delta (U21090), IP-30 (gamma-interferoninducible protein) (J03909, Lutheran blood group glycoprotein (X83425), tyrosine phosphatatase 1 non-receptor (HG3187-HT3366), mestatasis-associated mta-1 (U35113), (RPS6KA2) ribosomal protein S6 kinase 2 (L06797), transcription factor mef2 alt. splice 2 (HG4668-HT5083), basic transcription factor 44 kDa (HG3748-HT4018), soluble guanylate cyclase large subunit (X66534), transcription factor ETR101 (M62831), orphan G-protein-coupled receptor (L06797), MHC Class II W52 (HG3576-HT3779), prostasin (L41351), M6 antigen (X64364), Mrp17 (X79865), Ly-GDI (GDP-dissociation inhibitor protein) (L20688), KH type splicing regulatory protein KSRP (U94832), Ia-associated invariant gamma-chain (M13560), HLA-DRB1 (MHC class II beta1) (M33600), transcriptional activator hSNF2b (D26156), USF2 (AD000684), SEP protein (X87904), nested protein (M34677), HOXA9 (class I homeoprotein) (U41813), BRG1 (transcriptional activator) (U29175), KIAA0075 (D38550), eIF3 (translational initiation factor) (U78525), KIAA0113 (D30755), HU-K5 (lysophospholipase homolog) (U67963), ADP/ATP tranlocase (J03592), inducible poly(A)-binding protein (U33818), KIAA0146 (D63480), NET1 (guanine nucleotide regulatory protein) (U02081), KIAA0162 (D79984), v-ets erythroblastosis virus E26 oncogene like (AI351043), FBJ murine osteosarcroma viral oncogene homolog B (NM_—

006732.1), ubiquitin D (NM_—

006398.1), sialyltransferase I (AI743792), RALBP1 associated Eps domain containing 2 (NM_—

004726.1), chemokine (C-C motif) ligand 19 (U88321.1), transient receptor potential cation channel subfamily M member (NM_—

01736.1), B cell activation gen (S59049.1), eukaryotic translation initiation factor 4E binding protein 1 (AB044548.1), lymphocyte antigen 75 (NM_—

002349),

alpha-methylacyl-CoA racemase (NM_—

014324.1), phosphoprotein regulated by mitogenic pathway (NM_—

025195.1), RALBP1 associateds Eps domain containing 2 (NM_—

004726.1), neuropilin (NRP) and tolloid (TLL)-like 2 (NM_—

018092.1), twist homolog (X99268.1), calcium calmodulin-dependent protein kinase 2 (AA1181179), tumor associated calcium signal transducer 1 (NM_—

002354.1), UDP-N-acetylglucosamine phosphorylase I (S73498.1), epithelial cell transforming sequence 2 oncogene (NM_—

01898.1), myosin VI (U90236.2), LIM protein (NM_—

006457.1), claudin 8 (AL049977.1), phosphoprotein regulated by mitogenic pathway (NM_—

025195.1), thymosin beta (NM_—

021992.1), TNF (ligand) superfamily (U57059.1), unknown protein (AV715767), activated leucocyte cell adhesion molecule (NM_—

001627.1), chaperonin containing TCP1 (NM_—

001762.1), phosphoribosylaminoimidazole carboxylase (AA902652), protein (NM23A) (NM_—

000269.1); 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.

2. 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.

3. The method of claim 1 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

12. 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.

13. The method of claim 1 further comprising the step of determining the expression level of maspin (U04313) transcript or its translation product.

14. The method of claim 1 further comprising the step of determining the expression level of hepsin (X07732) transcript or its translation product.

15. The method of claim 1 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.

16. The method of claim 1 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.

17. The method of claim 1 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.

18. The method of claim 1 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.

19. The method of claim 1 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.

20. The method of claim 1 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.

21. The method of claim 1 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).

22. The method of claim 1 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).

23. The method of claim 1 wherein the test sample comprises Gleason grade 4/5 prostate carcinoma cells.

24. The method of claim 1 wherein the nonmalignant prostate tissue is benign prostate hyperplasia tissue.

25. The method of claim 1 further comprising the step of identifying the test sample as Gleason grade 4/5 prostate carcinoma.