Biomarkers for predicting prostate cancer progression

• US 20060234259A1
• Filed: 02/24/2006
• Published: 10/19/2006
• Est. Priority Date: 02/25/2005
• Status: Active Grant

• Current Assignee: Brigham and Women's Hospital Incorporated
• Original Assignee: Brigham and Women's Hospital Incorporated
• Inventors: Demichelis, Francesca, Rubin, Mark A.
• Granted Patent: US 7,666,595 B2
• 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 2600/118 Prognosis of disease development
• CPC Class Codes: C12Q 2600/136 Screening for pharmacological compounds
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: G01N 2500/10 involving cells
• CPC Class Codes: G01N 33/57434 of prostate

Abstract

The present invention relates to the identification and use of gene expression profiles with clinical relevance to prostate cancer. In particular, the invention provides the identity of genes whose expression, at the transcriptional and protein levels, is correlated with prostate cancer progression. Methods and kits are described for using these gene expression profiles in the study and/or diagnosis of prostate cancer diseases, in the prediction of prostate cancer progression, and in the selection and/or monitoring of treatment regimens. The invention also relates to the screening of drugs that target these genes or their protein products, in particular for the development of therapeutics for modulating prostate cancer progression.

Claims

1. A method for characterizing prostate tissue in a subject, comprising steps of:

providing a sample of prostate tissue obtained from the subject; and

determining the levels of expression of a set of genes selected from the group consisting of ABP280 (FLNA), AMACR, AR, BM28, BUB3, CaMKK, CASPASE3, CDK7, DYNAMIN, E2F1, E-CADHERIN, EXPORTIN, EZH2, FAS, GAS7, GS28, ICBP90, ITGA5, JAGGED1, JAM1, KANADAPTIN, KLF6, KRIP1, LAP2, MCAM, MIB1 (MKI67), MTA1, MUC1, MYOSIN-VI, P27, P63, PAXILLIN, PLCLN,

PSA(KLK3), RAB27, RBBP, RIN1, SAPKalpha, TPD52, XIAP, and ZAG, to obtain a gene expression pattern for the prostate tissue sample, thereby characterizing the prostate tissue.

2. The method of claim 1, wherein the set of genes comprises 4 or more genes, 5 or more genes, 6 or more genes, 7 or more genes, 8 or more genes, 9 or more genes, 10 or more genes, 11 or more genes, 12 or more genes, or 15 or more genes.

3. The method of claim 1, wherein the set of genes consists of ABP280 (FLNA), AMACR, CDK7, ITGA5, JAGGED1, KANADAPTIN, MIB1 (MKI67), MTA1, MUC1, p63, PSA(KLK3), and TPD52.

4. The method of claim 2, wherein determining the levels of expression of a set of genes comprises detecting the expression of mRNA expressed from said genes.

5. The method of claim 4, wherein determining the expression of mRNA comprises exposing said mRNA to a nucleic acid probe complementary to said mRNA.

6. The method of claim 2, wherein determining the levels of expression of a set of genes comprises detecting the expression of a polypeptide encoded by said genes.

7. The method of claim 6, wherein detecting the expression of a polypeptide comprises exposing the polypeptide to an antibody specific to said polypeptide and detecting the binding of said antibody to said polypeptide.

8. The method of claim 2, wherein the prostate tissue sample is a fixed, paraffin-embedded tissue sample, a fresh tissue sample, or a frozen tissue sample.

9. The method of claim 2, wherein the prostate tissue sample is a needle, core or other types of biopsy.

10. The method of claim 2, wherein characterizing the prostate tissue further comprises the step of:

identifying the prostate tissue as benign prostate tissue, localized prostate cancer, hormone naï

ve metastatic prostate cancer, hormone refractory metastatic prostate cancer, or metastatic small cell prostate cancer, based on the gene expression pattern obtained.

11. The method of claim 10, wherein identifying the prostate tissue comprises steps of:

comparing the gene expression pattern obtained to at least one prostate disease expression profile map, wherein the prostate disease expression profile map comprises gene expression level information for said set of genes in a particular type of prostate disease;

determining the degree of similarity between the gene expression pattern obtained and the expression profile map; and

based on the degree of similarity, identifying the prostate tissue.

12. The method of claim 11, wherein the particular type of prostate disease is selected from the group consisting of benign prostate disease, localized prostate cancer, hormone naive metastatic prostate cancer, hormone refractory metastatic prostate cancer, and metastatic small cell prostate cancer.

13. A method for providing a prognosis to a subject diagnosed with prostate disease, said method comprising steps of:

providing a sample of prostate tissue obtained from the subject;

determining the levels of expression of a set of genes selected from the group consisting of ABP280 (FLNA), AMACR, AR, BM28, BUB3, CaMKK, CASPASE3, CDK7, DYNAMIN, E2F1, E-CADHERIN, EXPORTIN, EZH2, FAS, GAS7, GS28,

ICBP90, ITGA5, JAGGED1, JAM1, KANADAPTIN, KLF6, KRIP1, LAP2, MCAM, MIB1 (MKI67), MTA1, MUC1, MYOSIN-VI, P27, P63, PAXILLIN, PLCLN, PSA(KLK3), RAB27, RBBP, RIN1, SAPKalpha, TPD52, XIAP, and ZAG, to obtain a gene expression pattern for the sample; and

based on the gene expression pattern obtained, providing a prognosis to the subject.

14. The method of claim 13, wherein the set of genes comprises 4 or more genes, 5 or more genes, 6 or more genes, 7 or more genes, 8 or more genes, 9 or more genes, 10 or more genes, 11 or more genes, 12 or more genes, or 15 or more genes.

15. The method of claim 14, wherein the set of genes consists of ABP280 (FLNA), AMACR, CDK7, ITGA5, JAGGED1, KANADAPTIN, MIB1 (MKI67), MTA1, MUC1, p63, PSA(KLK3), and TPD52.

16. The method of claim 14, wherein determining the levels of expression of a set of genes comprises detecting the expression of mRNA expressed from said genes.

17. The method of claim 16, wherein determining the expression of mRNA comprises exposing said mRNA to a nucleic acid probe complementary to said mRNA.

18. The method of claim 14, wherein determining the levels of expression of a set of genes comprises detecting the expression of a polypeptide encoded by said genes.

19. The method of claim 18, wherein detecting the expression of a polypeptide comprises exposing the polypeptide to an antibody specific to said polypeptide and detecting the binding of said antibody to said polypeptide.

20. The method of claim 14, wherein the prostate tissue sample is a fixed, paraffin-embedded tissue sample, a fresh tissue sample, or a frozen tissue sample.

21. The method of claim 14, wherein the prostate tissue sample is a needle, core or other types of biopsy.

22. The method of claim 14, wherein providing a prognosis comprises comparing the gene expression pattern obtained to at least one prostate disease expression profile map.

23. The method of claim 22, wherein the prostate disease expression profile map comprises gene expression level information for said set of genes for a particular type of prostate disease selected from the group consisting of benign prostate disease, localized prostate cancer, hormone naive metastatic prostate cancer, hormone refractory metastatic prostate cancer, and metastatic small cell prostate cancer.

24. The method of claim 14, wherein providing a prognosis comprises one or more of:

predicting prostate disease progression.

25. The method of claim 24, wherein predicting prostate disease progression comprises one or more of determining the likelihood of developing prostate cancer, determining the likelihood of developing aggressive prostate cancer, determining the likelihood of developing metastatic prostate cancer and determining long-term survival outcome.

26. The method of claim 14, further comprising the step of:

selecting a treatment regimen for the subject, based on the prognosis provided.

27. A prostate disease expression profile map comprising gene expression level information for a set of genes selected from the group consisting of ABP280 (FLNA), AMACR, AR, BM28, BUB3, CaMKK, CASPASE3, CDK7, DYNAMIN, E2F1, E-CADHERIN, EXPORTIN, EZH2, FAS, GAS7, GS28, ICBP90, ITGA5, JAGGED1, JAM1, KANADAPTIN, KLF6, KRIP1, LAP2, MCAM, MIB1 (MKI67), MTA1, MUC1, MYOSIN-VI, P27, P63, PAXILLIN, PLCLN, PSA(KLK3), RAB27, RBBP, RIN1, SAPKalpha, TPD52, XIAP, and ZAG.

28. The expression profile map of claim 27, wherein the set of genes comprises 4 or more genes, 5 or more genes, 6 or more genes, 7 or more genes, 8 or more genes, 9 or more genes, 10 or more genes, 11 or more genes, 12 or more genes, or 15 or more genes.

29. The expression profile map of claim 27, wherein the set of genes consists of ABP280 (FLNA), AMACR, CDK7, ITGA5, JAGGED1, KANADAPTIN, MIB1 (MKI67), MTA1, MUC1, p63, PSA(KLK3), and TPD52.

30. The expression profile map of claim 28, wherein the prostate disease is benign prostate disease, localized prostate cancer, hormone naï

ve metastatic prostate cancer, hormone refractory metastatic prostate cancer or metastatic small cell prostate cancer.

31. The expression profile map of claim 30, wherein the map is digital information stored in a computer-readable medium.

45. The kit of claim 38 further comprising at least one prostate disease expression profile map of claim 27.

46. The kit of claim 40 further comprising at least one prostate disease expression profile map of claim 29.

32. A prostate disease prognostic portfolio comprising isolated nucleic acid sequences, their complements, or portions thereof, of a set of genes selected from the group consisting of ABP280 (FLNA), AMACR, AR, BM28, BUB3, CaMKK, CASPASE3, CDK7, DYNAMIN, E2F1, E-CADHERIN, EXPORTIN, EZH2, FAS, GAS7, GS28, ICBP90, ITGA5, JAGGED1, JAM1, KANADAPTIN, KLF6, KRIP1, LAP2, MCAM, MIB1 (MKI67), MTA1, MUC1, MYOSIN-VI, P27, P63, PAXILLIN, PLCLN, PSA(KLK3), RAB27, RBBP, RIN1, SAPKalpha, TPD52, XIAP, and ZAG.

33. The prostate disease prognostic portfolio of claim 32, wherein the set of genes comprises 4 or more genes, 5 or more genes, 6 or more genes, 7 or more genes, 8 or more genes, 9 or more genes, 10 or more genes, 11 or more genes, 12 or more genes, or 15 or more genes.

34. The prostate disease prognostic portfolio of claim 32, wherein the set of genes consists of ABP280 (FLNA), AMACR, CDK7, ITGA5, JAGGED1, KANADAPTIN, MIB1 (MKI67), MTA1, MUC1, p63, PSA(KLK3), and TPD52.

35. The prostate disease prognostic portfolio of claim 33 in a matrix suitable for determining the expression levels of the genes contained therein.

36. The prostate disease prognostic portfolio of claim 35, wherein the matrix is employed in a microarray.

37. The prostate disease prognostic portfolio of claim 36, wherein the microarray is a cDNA microarray or an oligonucleotide microarray.

38. A kit for predicting prostate disease progression in a subject diagnosed with a prostate disease, said kit comprising:

at least one reagent that specifically detects expression levels of a set of genes selected from the group consisting of ABP280 (FLNA), AMACR, AR, BM28, BUB3, CaMKK, CASPASE3, CDK7, DYNAMIN, E2F1, E-CADHERIN, EXPORTIN, EZH2, FAS, GAS7, GS28, ICBP90, ITGA5, JAGGED1, JAM1, KANADAPTIN, KLF6, KRIP1, LAP2, MCAM, MIB1 (MKI67), MTA1, MUC1, MYOSIN-VI, P27, P63,

PAXILLIN, PLCLN, PSA(KLK3), RAB27, RBBP, RIN1, SAPKalpha, TPD52, XIAP, and ZAG; and

instructions for using said kit for predicting prostate disease progression in the subject.

39. The kit of claim of claim 38, wherein the set of genes comprises 4 or more genes, 5 or more genes, 6 or more genes, 7 or more genes, 8 or more genes, 9 or more genes, 10 or more genes, 11 or more genes, 12 or more genes, or 15 or more genes.

40. The kit of claim 38, wherein the set of genes consists of ABP280 (FLNA), AMACR, CDK7, ITGA5, JAGGED1, KANADAPTIN, MIB1 (MKI67), MTA1, MUC1, p63, PSA(KLK3), and TPD52.

41. The kit of claim 39, wherein said at least one reagent comprises a nucleic acid probe complementary to mRNA expressed from said set of genes.

42. The kit of claim 41, wherein the nucleic acid probe complementary to mRNA is cDNA or an oligonucleotide.

43. The kit of claim 41, wherein the nucleic acid probe complementary to mRNA is immobilized on a substrate surface.

44. The kit of claim 39, wherein said at least one reagent comprises an antibody that specifically binds to a polypeptide encoded by said set of genes.

47. A method for identifying a compound potentially useful to modulate prostate disease progression, said method comprising steps of:

providing a prostate cell or cell lysate sample;

incubating the cell or cell lysate sample with a candidate compound under certain conditions and for a certain time to obtain a test sample;

incubating the cell or cell lysate under the same conditions and for the same time absent the candidate compound to obtain a control sample;

determining, in the test sample, the levels of expression of a set of genes selected from the group consisting of ABP280 (FLNA), AMACR, AR, BM28, BUB3, CaMKK, CASPASE3, CDK7, DYNAMIN, E2F1, E-CADHERIN, EXPORTIN, EZH2, FAS,

GAS7, GS28, ICBP90, ITGA5, JAGGED1, JAM1, KANADAPTIN, KLF6, KRIP1, LAP2, MCAM, MIB1 (MKI67), MTA1, MUC1, MYOSIN-VI, P27, P63, PAXILLIN, PLCLN, PSA(KLK3), RAB27, RBBP, RIN1, SAPKalpha, TPD52, XIAP, and ZAG to obtain a gene expression pattern for the test sample;

determining, in the control sample, the levels of expression of the same set of genes to obtain a gene expression pattern for the control sample; and

identifying the candidate compound as a compound potentially useful to modulate prostate disease progression if the gene expression pattern of the test sample and the gene expression pattern of the control sample are different.

48. A method of claim 47, wherein the set of genes comprises 4 or more genes, 5 or more genes, 6 or more genes, 7 or more genes, 8 or more genes, 9 or more genes, 10 or more genes, 11 or more genes, 12 or more genes, or 15 or more genes.

49. The method of claim 47, wherein the set of genes consists of ABP280 (FLNA), AMACR, CDK7, ITGA5, JAGGED1, KANADAPTIN, MIB1 (MKI67), MTA1, MUC1, p63, PSA(KLK3), and TPD52.