Biomarkers for predicting prostate cancer progression
The present invention relates to biomarkers, methods and assay kits for predicting prognosis and/or monitoring progression of prostate cancer. The biomarkers include a glycosyltransferases [core 1 beta-3-galactosyltransferase (C1GALT1) and/or ST3 beta-galactoside alpha-2,3-sialyltransferase 1 (ST3GAL1)] gene product, its saccharide substrate/product, and/or a galectin-4 gene product.
1. A method for predicting prognosis of prostate cancer, comprising
(i) providing a prostate tumor sample from a subject afflicted with prostate cancer; and
(ii) detecting a core 1 beta-3-galactosyltransferase (C1GALT1) gene product and a galectin-4 gene product in the prostate tumor sample; and
(iii) comparing the results of the detection with a reference level and predicting prognosis for the subject based on the results of the comparison, wherein an elevated level of both the C1GALT1 gene product and the galectin-4 gene product is indicative of a more negative prognosis when compared to an elevated level of the C1GALT1 gene product alone or an elevated level of the galectin-4 gene product alone.
2. The method of claim 1 , wherein the gene product includes a protein or a RNA transcript.
3. The method of claim 1 , wherein the C1GALT1 gene product is detected with a first agent that specifically binds to the C1GALT1 gene product, and the galectin-4 gene product is detected with a second agent that specifically binds to the galectin-4 gene product.
4. The method of claim 3 , wherein the first agent is an antibody and/or the second agent is an antibody.
5. The method of claim 1 , wherein the detection is performed by a mass spectrometric assay or an immunoassay.
6. The method of claim 1 , wherein the negative prognosis is selected from the group consisting of a reduced survival rate, an increased tumor size or number, an increased risk of metastasis, an increased risk of resistance to androgen deprivation therapy (ADT), an increased risk of relapse, and any combination thereof.
7. A method for monitoring progression of prostate cancer in a patient afflicted with prostate cancer, comprising
(a) providing a first prostate tumor sample from the patient at a first time point;
(b) providing a second prostate tumor sample from the patient at a second time point, which is later than the first time point;
(c) detecting the levels of a C1GALT1 gene product and a galectin-4 gene product in the first and second samples; and
(d) determining prostate cancer progression in the patient based on the levels of the C1GALT1 gene product and the galectin-4 gene product in the first and second samples, wherein an elevated level of both the C1GALT1 gene product and the galectin-4 gene product in the second sample as compared to that in the first sample is indicative of a higher risk for prostate cancer progression when compared to an elevated level of the C1GALT1 gene product alone or an elevated level of the galectin-4 gene product alone in the second sample as compared to that in the first sample.
8. The method of claim 7 , wherein the gene product includes a protein or a RNA transcript.
9. The method of claim 7 , wherein the C1GALT1 gene product is detected with a first agent that specifically binds to the C1GALT1 gene product, and the galectin-4 gene product is detected with a second agent that specifically binds to the galectin-4 gene product.
10. The method of claim 9 , wherein the first agent is an antibody and/or the second agent is an antibody.
11. The method of claim 7 , wherein the detection is performed by a mass spectrometric assay or an immunoassay.
12. A method for predicting survival of prostate cancer, comprising
(i) providing a prostate tumor sample from a patient afflicted with prostate cancer;
(ii) detecting a level of a core 1 beta-3-galactosyltransferase (C1GALT1) mRNA and a level of a galectin-4 mRNA in the prostate tumor sample using quantitative RT-PCR;
(iii) comparing the detected level of the C1GALT1 mRNA with a reference level of C1GALT1 mRNA from a healthy prostate sample, and comparing the detected level of the galectin-4 mRNA with a reference level of galectin-4 mRNA from a healthy prostate sample;
(iv) predicting survival of the patient based on the comparison, including predicting a relatively higher risk for poor survival of the patient if the detected level of C1GALT1 mRNA in the prostate tumor sample exceeds the reference level of C1GALT1 mRNA and the detected level of galectin-4 mRNA in the prostate tumor sample exceeds the reference level of galectin-4, and otherwise predicting a relatively lower risk for poor survival of the patient if the detected level of C1GALT1 mRNA in the prostate tumor sample exceeds the reference level of C1GALT1 mRNA but the detected level of galectin-4 mRNA in the prostate tumor sample does not exceed the reference level of galectin-4, the detected level of galectin-4 mRNA in the prostate tumor sample exceeds the reference level of galectin-4 mRNA but the detected level of C1GALT1 mRNA in the prostate tumor sample does not exceed the reference level of C1GALT1, or the detected level of C1GALT1 mRNA in the prostate tumor sample does not exceed the reference level of C1GALT1 mRNA and the detected level of galectin-4 mRNA in the prostate tumor sample does not exceed the reference level of galectin-4.
13. The method of claim 12 , wherein the quantitative RT-PCR is carried out by using C1GALT1 forward primer 5′-TCCCTTTGTGCCAGAACACC (SEQ ID NO: 1) and C1GALT1 reverse primer 5′-AGCAACCAGGACCCTCTACA (SEQ ID NO: 2), and galectin-4 forward primer 5′-GATGCCACCTTACCCTGGTC (SEQ ID NO: 7) and galectin-4 reverse primer 5′-CCTTGCAGCCTCCCGAAATA (SEQ ID NO: 8).
14. The method of claim 12 , wherein
the patient has a hazard ratio (HR) of 15.8 for poor survival if the detected level of C1GALT1 mRNA in the prostate tumor sample exceeds the reference level of C1GALT1 mRNA and the detected level of galectin-4 mRNA in the prostate tumor sample exceeds the reference level of galectin-4;
the patient has a HR of 2.28 for poor survival if the detected level of C1GALT1 mRNA in the prostate tumor sample exceeds the reference level of C1GALT1 mRNA but the detected level of galectin-4 mRNA in the prostate tumor sample does not exceed the reference level of galectin-4; or
the patient of a low risk for poor survival has a HR of 2.975 for poor survival if the detected level of galectin-4 mRNA in the prostate tumor sample exceeds the reference level of galectin-4 mRNA but the detected level of C1GALT1 mRNA in the prostate tumor sample does not exceed the reference level of C1GALT1.