Prostate cancer prognostic compositions and kits

• US 9,951,390 B2
• Filed: 04/13/2016
• Issued: 04/24/2018
• Est. Priority Date: 12/24/2004
• Status: Active Grant

• Current Assignee: Stichting Katholieke Universiteit
• Original Assignee: Stichting Katholieke Universiteit
• Inventors: Hessels, Daphne, Verhaegh, Gerald, Schalken, Jack A., Witjes, J. Alfred
• Primary Examiner(s): Thomas, David C
• Application Number:
  US15/097,758
• Publication Number:
  US 20160362746A1
• Time in Patent Office: 741 Days
• Field of Search: None
• 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 2600/158 Expression markers
• CPC Class Codes: C12Q 2600/16 Primer sets for multiplex assays
• CPC Class Codes: G01N 2333/96455 Kallikrein (3.4.21.34; 3.4.21.35)
• CPC Class Codes: G01N 33/57434 of prostate

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.

Claims

1. A method for characterizing prostate cancer in a biological sample of a subject comprising:

a) synthesizing PCA3 cDNA from a prostate cancer specific PCA3 mRNA from the biological sample;

b) measuring the amount of the synthesized PCA3 cDNA;

c) measuring an amount of PSA in the biological sample; and

d) determining a ratio value of the amount of the synthesized PCA3 cDNA over the amount of PSA.

2. The method of claim 1, further comprising comparing the ratio value to at least one predetermined cut-off value.

3. The method of claim 2, 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;

or of the presence of a more aggressive cancer as compared to a ratio value below the predetermined cut-off value which is indicative of the presence of a less aggressive cancer.

4. The method of claim 2, wherein a ratio value above the predetermined cut-off value is indicative of a greater prostate cancer tumor volume as compared to a ratio value below the predetermined cut-off value;

or of a more advanced stage of prostate cancer as compared to a ratio value below the predetermined cut-off value.

5. The method of claim 1, wherein the ratio value is useful for estimating or determining a grade or stage of prostate cancer.

6. The method of claim 1, wherein the biological sample comprises urine, resected prostate tissue, biopsied prostate tissue, ejaculate, or a bladder washing.

7. The method of claim 1, wherein the amount of PSA is the amount of PSA mRNA.

8. The method of claim 1, wherein the PCA3 cDNA is synthesized in an amplification reaction.

9. The method of claim 8, wherein the amplification reaction comprises RT-PCR, transcription mediated amplification, nucleic acid sequence-based amplification, or strand displacement amplification.

10. The method of claim 1, wherein the amount of PSA is the amount of PSA protein.

11. The method of claim 1, wherein the biological sample is obtained from a patient undergoing a prostate cancer treatment.

12. The method of claim 11, wherein the ratio value is used to determine an effect of the treatment on the cancer or mortality risk.

13. The method of claim 1, wherein the subject has a serum PSA protein level of at least about 3 ng/ml.

14. A method for characterizing prostate cancer in a biological sample comprising:

a) contacting a biological sample with one or more first oligonucleotides that hybridize to a prostate cancer specific PCA3 mRNA or a complement thereof;

b) contacting the biological sample with one or more second oligonucleotides that hybridize to a PSA mRNA or a complement thereof;

c) determining the amount of PCA3 mRNA and the amount of PSA mRNA present in the biological sample;

d) determining a ratio value of the amount of PCA3 mRNA over the amount of PSA mRNA,

wherein the one or more first oligonucleotides comprise at least one of an artificially labeled oligonucleotide or a promoter-primer.

15. The method of claim 14, wherein the one or more first oligonucleotides comprise at least one oligonucleotide artificially labeled with a fluorescent, colorimetric, enzymatic, enzyme substrate, radioactive, bioluminescent, phosphorescent, affinity ligand, or homogeneous detectable label.

16. The method of claim 14, wherein the one or more first oligonucleotides comprise at least one promoter-primer.

17. The method of claim 14, wherein the one or more first oligonucleotides are used to amplify the prostate cancer specific PCA3 mRNA or complement thereof.

18. The method of claim 17, wherein the amplification reaction comprises polymerase chain reaction (PCR);

nucleic acid sequence-based amplification assay (NASBA);

transcription mediated amplification (TMA);

ligase chain reaction (LCR);

or strand displacement amplification (SDA).

19. The method of claim 14, wherein the amounts of the prostate cancer specific PCA3 nucleic acid and of the PSA nucleic acid are determined using a hybridization assay.

20. The method of claim 14, wherein the promoter-primer or artificially labeled oligonucleotide hybridizes to a PCA3 nucleic acid sequence comprising (i) the nucleic acid sequence set forth in SEQ ID NO:

1;

(ii) the nucleic acid sequence set forth in SEQ ID NO;

2;

or (iii) a nucleic acid sequence that hybridizes under high stringency conditions to a nucleic acid sequence in (i) or (ii).