Prostate cancer prognostic compositions and kits

Abstract

Described herein are method, compositions and kits for prognosis of prostate cancer. The methods include 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 method for prognosing prostate cancer in a sample of a patient includes 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.

What is claimed is: 
     
         1 . A method for treating prostate cancer in a patient comprising:
 (a) obtaining a first urine sample from said patient;   (b) performing a first hybridization and/or amplification assay on mRNA or cDNA derived from said urine sample using at least a first oligonucleotide specific for a prostate cancer associated PCA3 RNA or cDNA;   (c) determining the amounts of:
 (i) said prostate cancer associated PCA3 RNA or cDNA; 
 (ii) at least one further prostate cancer or neoplastic disease marker; and 
 (iii) a prostate-specific marker, 
   in said urine sample;   (d) determining a first ratio value of said amount of said prostate cancer associated PCA3 RNA or cDNA and said amount of further prostate cancer or neoplastic disease marker over said amount of prostate-specific marker;   e) comparing said first ratio value to at least one predetermined cut-off value;   f) identifying said patient as having a more aggressive prostate cancer when the first ratio value is above said at least one predetermined cut-off value; and   (g) administering to said patient a prostate cancer treatment for a more aggressive prostate cancer.   
     
     
         2 . The method of  claim 1 , wherein step (c)(ii) comprises (a) determining the amount of RNA or cDNA of said further prostate cancer or neoplastic disease marker and step (c)(iii) comprises (a) determining the amount of mRNA or cDNA of said prostate-specific marker. 
     
     
         3 . The method of  claim 2 , wherein step (c)(ii)(a) comprises performing a second hybridization and/or amplification assay on mRNA or cDNA derived from said sample using at least a second oligonucleotide specific for said prostate cancer or neoplastic disease marker RNA or cDNA and step (c)(iii)(a) comprises performing a third hybridization and/or amplification assay on mRNA or cDNA derived from said sample using at least a third oligonucleotide specific for said prostate specific marker. 
     
     
         4 . The method of  claim 3 , wherein said further prostate cancer or neoplastic disease marker is urinary plasminogen activator, urinary plasminogen activator receptor, plasminogen inhibitor 1, p53, E-cadherin, PSM or VEGF. 
     
     
         5 . The method of  claim 3 , further comprising (h) repeating steps (c) and (d) with a second urine sample from said patient obtained at a subsequent point in time to determine a second a second ratio value and comparing said first ratio and second ratio values, thereby assessing the efficacy of said prostate cancer treatment over time. 
     
     
         6 . A method for treating prostate cancer in a patient comprising:
 (a) obtaining a first urine sample from said patient;   (b) determining the amounts of:
 (i) a prostate cancer associated PCA3 mRNA or cDNA molecule; 
 (ii) a prostate cancer or neoplastic disease marker; and 
 (iii) a prostate-specific marker, 
   in a urine sample from said patient;   (c) normalizing the amounts of said PCA3 RNA or cDNA molecule and said prostate cancer or neoplastic disease marker to the amount of said prostate-specific marker; and   (d) comparing said normalized amounts of said PCA3 RNA or cDNA molecule and said prostate cancer specific marker to at least one predetermined cut-off value;   (e) identifying said patient as having a more aggressive prostate cancer when said normalized amounts are above said at least one predetermined cut-off value; and   (f) administering to said patient a prostate cancer treatment for a more aggressive prostate cancer.   
     
     
         7 . The method of  claim 6 , wherein step (b)(i) comprises performing a first hybridization and/or amplification assay on mRNA or cDNA derived from said sample using at least a first oligonucleotide specific for a prostate cancer associated PCA3 RNA or cDNA, wherein step (b)(ii) comprises performing a second hybridization and/or amplification assay on RNA or cDNA derived from said sample using at least a second oligonucleotide specific for said further prostate cancer or neoplastic disease marker; and wherein step (b)(iii) comprises performing a third a hybridization and/or amplification assay on RNA or cDNA derived from said sample using at least a third oligonucleotide specific for a prostate-specific marker. 
     
     
         8 . The method of  claim 7 , wherein an amplification reaction is used in steps (b)(i), (b)(ii) and (b)(iii). 
     
     
         9 . The method of  claim 6 , wherein the amount of said prostate cancer associated PCA3 RNA or cDNA is determined by using at least one oligonucleotide that hybridizes to a PCA3 nucleic acid sequence which is:
 (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).   
     
     
         10 . The method of  claim 9 , wherein said prostate-specific marker is PSA. 
     
     
         11 . The method of  claim 1 , wherein said urine sample is a urine sample obtained after a digital rectal examination. 
     
     
         12 . A method for treating prostate cancer in a patient comprising:
 (a) obtaining a first urine sample from said patient;   (b) determining the amounts of:
 (i) a prostate cancer associated PCA3 RNA or cDNA molecule; 
 (ii) a prostate cancer or neoplastic disease marker; and 
 (iii) a prostate-specific marker, 
   in a urine sample from said patient;   (c) normalizing the amounts of said PCA3 RNA molecule and said prostate cancer or neoplastic disease marker to the amount of said prostate-specific marker;   (d) repeating steps b) and c) using a second urine sample from said patient, wherein said second urine sample is obtained at a further point in time during therapy;   (e) comparing said normalized amounts of said PCA3 and of said prostate cancer or neoplastic disease marker in said first urine sample and said second urine sample;   (f) identifying said patient as having:
 aa) a more aggressive prostate cancer, bb) prostate cancer progression, cc) a prostate cancer of a higher grade; or dd) a prostate cancer of a higher stage, when said normalized amounts in said second urine sample obtained at a further point in time are above the normalized amounts of said first urine sample; and 
   (g) administering to said patient a prostate cancer treatment for a more aggressive prostate cancer.   
     
     
         13 . The method of  claim 12 , wherein step (b)(i) comprises performing a first hybridization and/or amplification assay on mRNA or cDNA derived from said sample using at least a first oligonucleotide specific for a prostate cancer associated PCA3 RNA or cDNA; wherein step (b)(ii) comprises performing a second hybridization and/or amplification assay on RNA or cDNA derived from said sample using at least a second oligonucleotide specific for said further prostate cancer or neoplastic disease marker; and wherein step (b)(iii) comprises performing a third a hybridization and/or amplification assay on RNA or cDNA derived from said sample using at least a third oligonucleotide specific for a prostate-specific marker. 
     
     
         14 . A method for treating prostate cancer in a patient comprising:
 (a) obtaining a urine sample from said patient;   (b) performing a first hybridization and/or amplification assay on RNA or cDNA derived from said sample using at least a first oligonucleotide specific for a prostate cancer associated PCA3 RNA or cDNA;   (c) determining the amount of said prostate cancer associated PCA3 RNA or cDNA and the amount of a prostate-specific marker, in said urine sample;   (d) determining the presence or amount of a further prostate cancer or neoplastic disease marker in said urine sample;   (e) determining a first ratio value of said amount of said prostate cancer associated PCA3 mRNA or cDNA and said amount of further prostate cancer or neoplastic disease marker over said amount of prostate-specific marker;   (f) comparing said first ratio value to at least one predetermined cut-off value;   (g) identifying said patient as having a more aggressive prostate cancer when the first ratio value is above said at least one predetermined cut-off value;   (h) administering to said patient a prostate cancer treatment for a more aggressive prostate cancer.   
     
     
         15 . The method of  claim 14 , wherein step (d) comprises determining the amount of said prostate cancer or neoplastic disease marker in the urine sample from said patient; and wherein said method further comprises determining a second ratio value of said prostate cancer or neoplastic disease marker over the amount of said prostate-specific marker, and comparing said second ratio value to at least one predetermined cut-off value. 
     
     
         16 . The method of  claim 15 , wherein step (c) comprises determining the amount of RNA or cDNA of said prostate specific marker and step (d) comprises determining the amount of RNA or cDNA of said prostate cancer or neoplastic disease marker. 
     
     
         17 . The method of  claim 15 , wherein said first ratio is compared to a first cut-off value and wherein said second ratio is compared to a second cut-off value different from said first cut-off value. 
     
     
         18 . The method of  claim 1 , wherein said prostate cancer associated PCA3 RNA or cDNA lacks intron 3 between exons 3 and 4a. 
     
     
         19 . The method of  claim 6 , wherein said prostate cancer associated PCA3 RNA or cDNA lacks intron 3 between exons 3 and 4a. 
     
     
         20 . The method of  claim 14 , wherein said prostate cancer associated PCA3 RNA or cDNA lacks intron 3 between exons 3 and 4a.