Prostate cancer-associated secreted proteins
Methods are provided for treating a subject with prostate cancer and/or diagnosing a subject at risk for prostate cancer, which can include measuring increased expression of at least two prostate cancer-related molecules in a sample obtained from a subject, including the prostate cancer-related molecules AGR2, AGR3, CRISP3, CCL3, CEACAM5, CEACAM6, IL24, MMP9, CXCL14, CD90, POSTN, and SFRP4. The methods can include administering at therapy to a subject with prostate cancer. Methods are provided for treating a subject with intermediate- or high-risk prostate cancer, which can include measuring increased expression of MMP9 in a sample obtained from a subject compared to a control representing expression of MMP9 expected in a sample from a subject who has low-risk prostate cancer.
1. A method of treating a subject with intermediate- or high-risk prostate cancer, comprising:
measuring protein expression of MMP9 in a sample obtained from a subject, comprising measuring at least one surrogate peptide of MMP9, wherein the at least one surrogate peptide of MMP9 consists of SEQ ID NO: 41 or -SEQ ID NO: 42;
measuring protein expression of PSA in the sample obtained from the subject;
normalizing the protein expression of MMP9 to the protein expression of PSA in the sample from the subject;
measuring increased protein expression of MMP9 normalized to PSA in the sample obtained from the subject as compared to a control representing protein expression of MMP9 normalized to PSA expected in a sample from a subject who has low-risk prostate cancer; and
administering treatment for intermediate- or high-risk prostate cancer to the subject, thereby treating the subject, wherein high-, intermediate-, and low-risk prostate cancer is defined by Gleason scoring.
2. The method of claim 1 , wherein the at least one surrogate peptide of MMP9 is measured using a mass spectrometry technique.
3. The method of claim 2 , wherein the mass spectrometry technique is liquid chromatography-selected reaction monitoring (LC-SRM); long gradient-selected reaction monitoring (LG-SRM); or high-pressure, high-resolution separations, intelligent selection, multiplexing-selected reaction monitoring (PRISM-SRM).
4. The method of claim 1 , wherein the at least one surrogate peptide of MMP9 protein is measured using an immunoassay.
5. The method of claim 4 , wherein the immunoassay is an ELISA.
6. The method of claim 1 , wherein normalizing to PSA protein expression comprises normalizing to at least one surrogate peptide of PSA.
7. The method of claim 6 , wherein the at least one surrogate peptide of PSA comprises SEQ ID NO: 70 or SEQ ID NO: 71.
8. The method of claim 1 , wherein the sample obtained from the subject is a urine sample.
9. The method of claim 1 , wherein the measured protein expression of MMP9 has an AUC value of greater than 0.8.
10. The method of claim 1 , wherein the measured protein expression of MMP9 has an AUC value of greater than 0.9.
11. The method of claim 1 , wherein administering treatment for intermediate- or high-risk prostate cancer comprises administering surgery, radiation therapy, chemotherapy, or hormone therapy.
12. The method of claim 1 , wherein the subject is human.
13. The method of claim 1 , wherein Gleason scoring is used to determine high-, intermediate-, and low-risk prostate cancer.
14. The method of claim 1 , wherein the high-risk prostate cancer is defined by a Gleason score greater than 7, the intermediate-risk prostate cancer is defined by a Gleason score of 7, and the low-risk prostate cancer is defined by a Gleason score less than or equal to 6.
15. A method of treating a subject with intermediate- or high-risk prostate cancer, comprising:
measuring protein expression of MMP9 in a urine sample obtained from a subject, comprising measuring at least one surrogate peptide of MMP9, wherein the at least one surrogate peptide of MMP9 consists of SEQ ID NO: 41 or SEQ ID NO: 42;
normalizing protein expression of MMP9 to PSA protein expression, wherein normalizing to PSA protein expression comprises normalizing to protein expression of at least one surrogate peptide of PSA;
measuring increased protein expression of MMP9 normalized to PSA in the urine sample obtained from the subject as compared to a control representing protein expression of MMP9 normalized to PSA expected in a urine sample from a subject who has low-risk prostate cancer; and
administering treatment for intermediate- or high-risk prostate cancer to the subject, thereby treating the subject, wherein high-, intermediate-, and low-risk prostate cancer is defined by Gleason scoring.
16. The method of claim 15 , wherein Gleason scoring is used to determine high-, intermediate-, and low-risk prostate cancer.
17. The method of claim 15 , wherein the high-risk prostate cancer is defined by a Gleason score greater than 7, the intermediate-risk prostate cancer is defined by a Gleason score of 7, and the low-risk prostate cancer is defined by a Gleason score less than or equal to 6.