Methods for Screening, Predicting and Monitoring Prostate Cancer

• US 20090226915A1
• Filed: 01/06/2009
• Published: 09/10/2009
• Est. Priority Date: 01/24/2001
• Status: Abandoned Application

• Current Assignee: Health Discovery Corporation
• Original Assignee: Health Discovery Corporation
• Inventors: Guyon, Isabelle
• Application Number:
  US12/349,437
• Publication Number:
  US 20090226915A1
• 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 2600/158 Expression markers
• CPC Class Codes: C12Q 2600/16 Primer sets for multiplex assays
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/57434 of prostate

Abstract

Biomarkers are identified by analyzing gene expression data using support vector machines (SVM) to rank genes according to their ability to separate prostate cancer from normal tissue. Expression products of identified genes are detected in patient samples, including prostate tissue, serum, semen and urine, to screen, predict and monitor prostate cancer.

Claims

1. A method for screening or monitoring a patient for prostate cancer, comprising:

obtaining a biological sample for the patient;

detecting within each of the biological sample and a control an expression level of a product of each of from one to four genes consisting of PDZ and LIM5 (SEQ ID NO.

     1), UAP1/AgX1 antigen (SEQ ID NO.

     2), HSPD1/chaperonin (SEQ ID NO.

     3), IMPDH2 (SEQ ID NO.

     5);

detecting within the biological sample and the control an expression level of a product of a reference gene;

normalizing the expression level of the product of each of the from one to four genes using the expression level of the product of the reference gene;

classifying the biological sample as “

cancer”

or “

normal”

by generating a binary prediction score by combining the normalized expression level of all of the from one to four genes with a bias.

2. The method of claim 1, wherein the biological sample comprises urine and the expression products of the from one to four genes comprise proteins PDZ and LIM5 (SEQ ID NO. 19), UAP1/AgX1 antigen (SEQ ID NO. 20), HSPD1/chaperonin (SEQ ID NO. 21) and IMPDH2 (SEQ ID NO. 22).

3. The method of claim 1, wherein the biological sample comprises urine and the expression products of the from one to four genes comprises two proteins consisting of PDZ and LIM5 (SEQ ID NO. 19) and UAP1/AgX1 antigen (SEQ ID NO. 20).

4. The method of claim 1, wherein the biological sample comprises urine and the expression product of the from one to four genes comprises PDZ and LIM5 (SEQ ID NO. 19).

5. The method of claim 1, wherein a prediction score is determined according to the relationship

S=ln(HSPD1/ref.gene)+ln(IMPDH2/ref.gene)+ln(PDLIM5/ref.gene)+ln(UAP1/ref.gene)+b,

where ref gene is the reference gene and b is the bias value, and wherein a positive value of S indicates the presence of cancer in the biological sample and negative value corresponds to the absence of cancer in the biological sample.

6. The method of claim 5, wherein the reference gene is B2M.

7. The method of claim 1, wherein a magnitude of the prediction score comprises a measure of confidence in a classification as cancer or not cancer.

8. A method for predicting a clinical outcome in response to a treatment of a prostate cancer, the method comprising the steps of:

(1) measuring expression levels of expression products of from one to four prognostic genes selected from the group consisting of PDZ and LIM5 (SEQ ID NO.

     1), UAP1/AgX1 antigen (SEQ ID NO.

     2), HSPD1/chaperonin (SEQ ID NO.

     3), F5 (SEQ ID NO.

     4), IMPDH2 (SEQ ID NO.

     5), PPIB (SEQ ID NO.

     6), RGS10 (SEQ ID NO.

     9) and PYCR1 (SEQ ID NO.

     10) in tissue, serum, semen or urine from a patient; and

(2) comparing each of the expression levels to a corresponding control level, wherein the result of the comparison is predictive of a clinical outcome.

9. The method of claim 8, wherein the biological sample comprises urine and the from one to four genes comprises four genes consisting of PDZ and LIM5 (SEQ ID NO. 1), UAP1/AgX1 antigen (SEQ ID NO. 2), HSPD1/chaperonin (SEQ ID NO. 3) and IMPDH2 (SEQ ID NO. 5).

10. The method of claim 8, wherein the biological sample comprises urine and the from one to four genes comprises two genes consisting of PDZ and LIM5 (SEQ ID NO. 1) and UAP1/AgX1 antigen (SEQ ID NO. 2).

11. The method of claim 8, wherein the biological sample comprises urine and the from one to four genes comprises PDZ and LIM5 (SEQ ID NO. 1).

12. The method of claim 8, wherein a prediction score is used to classify the biological sample as cancer or non-cancer, wherein the prediction score is determined according to the relationship

S=ln(HSPD1/ref.gene)+ln(IMPDH2/ref.gene)+ln(PDLIM5/ref.gene)+ln(UAP1/ref.gene)+b,

where ref gene is a reference gene and b is a bias value, and wherein a positive value of S indicates the presence of cancer in the biological sample and negative value corresponds to the absence of cancer in the biological sample.

13. The method of claim 12, wherein the ref.gene is B2M.

14. The method of claim 12, wherein a magnitude of S comprises a measure of confidence in a classification as cancer or not cancer.

15. A method of detecting the presence or absence of prostate cancer in a subject, comprising:

a) providing a biological sample from the subject;

b) providing a reagent for detecting from one to four expression products selected from a group of genes consisting of PDZ and LIM5 (SEQ ID NO.

     1), UAP1/AgX1 antigen (SEQ ID NO.

     2), HSPD1/chaperonin (SEQ ID NO.

     3), F5 (SEQ ID NO.

     4), IMPDH2 (SEQ ID NO.

     5), PPIB (SEQ ID NO.

     6), RGS10 (SEQ ID NO.

     9) and PYCR1 (SEQ ID NO.

     10);

c) contacting the biological sample with the reagent under conditions such that said reagent detects the presence or absence of the from one to four expression products in the biological sample;

d) determining the presence or absence of prostate cancer in said subject based on the presence or absence of the from one to four expression products in the biological sample.

16. The method of claim 15, wherein the biological sample comprises urine and the from one to four marker genes comprises four marker genes consisting of PDZ and LIM5 (SEQ ID NO. 1), UAP1/AgX1 antigen (SEQ ID NO. 2), HSPD1/chaperonin (SEQ ID NO. 3) and IMPDH2 (SEQ ID NO. 5).

17. The method of claim 15, wherein the biological sample comprises urine and the from one to four marker genes comprises two marker genes consisting of PDZ and LIM5 (SEQ ID NO. 1) and UAP1/AgX1 antigen (SEQ ID NO. 2).

18. The method of claim 15, wherein the biological sample comprises urine and the from one to four marker genes comprises PDZ and LIM5 (SEQ ID NO. 1).

19. The method of claim 15, wherein a prediction score is used to classify the biological sample as cancerous or non-cancerous, wherein the prediction score is determined according to the relationship

S=ln(HSPD1/ref.gene)+ln(IMPDH2/ref.gene)+ln(PDLIM5/ref.gene)+ln(UAP1/ref.gene)+b,

where ref gene is a reference gene and b is a bias value, and wherein a positive value of S indicates the presence of cancer in the biological sample and negative value corresponds to the absence of cancer in the biological sample.

20. The method of claim 15, wherein a magnitude of S comprises a measure of confidence in a classification as cancer or not cancer.