Prostate cancer prognostic compositions and kits

Abstract

Described herein are method, compositions and kits for prognosis of prostate cancer. The methods comprise: determining the ratio of PCA3 and of a prostate-specific marker expression in a urine sample and correlating the value of the PCA3/prostate-specific marker ratio with the aggressiveness and mortality risk of prostate cancer in the subject. The present invention features a method for prognosing prostate cancer in a sample of a patient comprising: assessing the amount of a prostate cancer specific PCA3 mRNA and the amount of prostate-specific marker in the sample; determining a ratio value of this amount of prostate cancer specific PCA3 mRNA over the amount of prostate-specific marker; comparing the ratio value to at least one predetermined cut-off value, wherein a ratio value above the predetermined cut-off value is indicative of a higher risk of mortality of prostate cancer as compared to a ratio value below the predetermined cut-off value.

1 . A prostate cancer prognostic composition comprising:
 (a) at least one prostate cell or a nucleic acid extract thereof, from a biological sample from a subject having or suspected of having prostate cancer;   (b) reagents for determining the amount of a prostate cancer associated PCA3 RNA in said biological sample; and   (c) reagents for normalizing said amount of prostate cancer associated PCA3 RNA in said biological sample.   
     
     
         2 . The prostate cancer prognostic composition of  claim 1 , wherein said reagents in (c) comprise reagents for determining the amount of a prostate-specific marker in said biological sample. 
     
     
         3 . The prostate cancer prognostic composition of  claim 1 , wherein said at least one prostate cell or nucleic acid extract thereof is from: urine, prostate tissue resection, prostate tissue biopsy, ejaculate or bladder washing. 
     
     
         4 . The prostate cancer prognostic composition of  claim 1 , wherein said at least one prostate cell or nucleic acid extract thereof is from urine obtained after a digital rectal examination. 
     
     
         5 . The prostate cancer prognostic composition of  claim 1 , wherein said at least one prostate cell or nucleic acid extract thereof is from urine obtained not directly following a digital rectal examination. 
     
     
         6 . The prostate cancer prognostic composition of  claim 1 , wherein said reagents in (b) and (c) enable an amplification and/or hybridization reaction to be performed. 
     
     
         7 . The prostate cancer prognostic composition of  claim 6 , wherein said amplification reaction is:
 (1) polymerase chain reaction (PCR);   (2) nucleic acid sequence-based amplification assay (NASBA);   (3) transcription mediated amplification (TMA);   (4) ligase chain reaction (LCR); or   (5) strand displacement amplification (SDA).   
     
     
         8 . The prostate cancer prognostic composition of  claim 1 , wherein said reagents in (b) comprise at least one oligonucleotide that specifically hybridizes to said prostate cancer associated PCA3 RNA. 
     
     
         9 . The prostate cancer prognostic composition of  claim 2 , wherein said reagents in (c) enable the detection of prostate-specific marker RNA. 
     
     
         10 . The prostate cancer prognostic composition of  claim 9 , wherein said reagents in (c) comprise at least one oligonucleotide that specifically hybridizes to said prostate-specific marker. 
     
     
         11 . The prostate cancer prognostic composition of  claim 10 , wherein said at least one oligonucleotide that specifically hybridizes to said prostate cancer associated PCA3 RNA specifically hybridizes to:
 (a) a nucleic acid sequence set forth in SEQ ID NO: 1;   (b) a nucleic acid sequence set forth in SEQ ID NO: 2; or   (c) a nucleic acid sequence that hybridizes under high stringency conditions to a nucleic acid sequence in (a) or (b).   
     
     
         12 . The prostate cancer prognostic composition of  claim 2 , wherein said reagents in (c) enable the detection of prostate-specific marker protein. 
     
     
         13 . The prostate cancer prognostic composition of  claim 12 , wherein said reagents in (c) comprise an antibody that specifically binds to said prostate-specific marker protein. 
     
     
         14 . The prostate cancer prognostic composition of  claim 2 , wherein said prostate-specific marker is: HK2/KLK2, PSMA, transglutaminase 4, acid phosphatase, PCGEM1, NKX3.1, prostate stem cell antigen (PSCA), prostate tumor inducing gene-1 (PTI-1), PDEF, TMPRSS2 or Prostase. 
     
     
         15 . A prostate cancer prognostic kit comprising:
 (a) reagents for determining the amount of a prostate cancer associated PCA3 RNA in a biological sample of a patient;   (b) reagents for normalizing said amount of prostate cancer associated PCA3 RNA in said biological sample; and   (c) information to correlate said normalized amount of prostate cancer associated PCA3 RNA to a prognosis of prostate cancer in said patient.   
     
     
         16 . The prostate cancer prognostic kit of  claim 15 , wherein said reagents in (a) comprise at least one oligonucleotide that specifically hybridizes to said prostate cancer associated PCA3 RNA. 
     
     
         17 . The prostate cancer prognostic kit of  claim 15 , wherein said reagents for normalizing in (b) comprise at least one oligonucleotide that specifically hybridizes to a prostate-specific marker RNA. 
     
     
         18 . The prostate cancer prognostic kit of  claim 16 , wherein said at least one oligonucleotide that specifically hybridizes to said prostate cancer associated PCA3 RNA specifically hybridizes to:
 (a) a nucleic acid sequence set forth in SEQ ID NO: 1;   (b) a nucleic acid sequence set forth in SEQ ID NO: 2; or   (c) a nucleic acid sequence that hybridizes under high stringency conditions to a nucleic acid sequence in (a) or (b).   
     
     
         19 . The prostate cancer prognostic composition of  claim 12 , wherein said prostate-specific marker is a prostate-specific marker protein and said reagents in (b) comprise an antibody that specifically binds to said prostate-specific marker protein. 
     
     
         20 . The prostate cancer prognostic kit of  claim 17 , wherein said prostate-specific marker is: HK2/KLK2, PSMA, transglutaminase 4, acid phosphatase, PCGEM1, NKX3.1, prostate stem cell antigen (PSCA), prostate tumor inducing gene-1 (PTI-1), PDEF, TMPRSS2 or Prostase.