Prognostic Value of Prostate Secretory Protein of 94 Amino Acids and its Binding Protein after Radical Prostatectomy

Abstract

Purpose: To establish the prognostic value of total and free prostate secretory protein of 94 amino acids (PSP94) and the PSP94-binding protein (PSPBP) following radical prostatectomy. Experimental Design: One hundred and eighty-five serum samples were obtained from patients with localized prostate cancer prior to treatment with radical prostatectomy at Virginia Urology (Richmond, VA). Patients were followed up for a median of 48 months (range, 1-66 months) and biochemical relapse was indicated as total prostate-specific antigen (tPSA) levels increasing to >0.1 ng/mL. The available clinical variables included initial tPSA, Gleason score, surgical margin status, and clinical stage. Total PSP94, free PSP94, and the PSPBP were quantified in the pretreatment serum using new ELISA tests (Medicorp, Inc. and Ambrilia Biopharma, Inc., Montreal, Quebec, Canada). Univariate and multivariate Cox proportional hazards models were used to assess the ability of PSP94 and PSPBP to predict time to recurrence. Results: Thirty-one patients had biochemical recurrence. Gleason score, margin status, clinical stage, and initial tPSA significantly predicted recurrence risk (all P < 0.001). In addition, PSPBP was negatively associated with recurrence risk (P = 0.005), and, consistent with previous studies, the bound/free PSP94 ratio was positively associated with recurrence risk (P = 0.008). Multivariate analysis showed that PSPBP, as well as the bound/free PSP94 ratio, were independent predictors of biochemical relapse risk adjusting for tPSA, Gleason score, and margin status. Conclusions: Bound/free PSP94 and PSPBP are novel and independent prognostic markers following radical prostatectomy for prostate cancer.

New circulating biomarkers for prostate cancer

“…In a recent study, PSBP and the ratio of bound PSP94/free PSP94 were independent predictors of biochemical recurrence in patients who underwent radical prostatectomy, after adjustment for total PSA, Gleason sum and surgical margin status. 92 However, further large prospective studies are warranted to confirm these preliminary findings.…”

Prognostic Significance of Prostate Cancer Susceptibility Variants on Prostate-Specific Antigen Recurrence after Radical Prostatectomy

“…More recently, prostatic secretory protein 94 has been found to circulate in blood with low-(free prostatic secretory protein 94) and high (bound to prostatic secretory protein 94-binding protein)-molecular weight forms (25). In the prostate cancer patients who have undergone radical prostatectomy, the bound/free prostatic secretory protein 94 ratio was positively associated with the risk for recurrence after adjusting for prostate-specific antigen, Gleason score, and margin status (26). Furthermore, MSMB is thought to be a tumor suppressor (27) possibly capable of impeding prostate cancer growth, promoting apoptosis, inhibiting the secretion of matrix metalloproteinase implicated in tumor metastasis, and decreasing vascular endothelial growth factor-mediated vascularization.…”

Effect of androgen deprivation therapy on the expression of prostate cancer biomarkers MSMB and MSMB-binding protein CRISP3

“…[13][14][15] Serum levels of MSMB, its binding protein PSP94-binding protein (PSPBP) and the ratio free/bound MSMB, have all been suggested as independent prognostic factors in prostate cancer. [16][17][18][19] We have previously reported that the cysteine-rich secretory family (CRISP) family member CRISP3 also forms a high-affinity complex with MSMB in human seminal plasma. 20 CRISP3 has been found to be one of the most upregulated genes in prostate cancer compared to benign tissue, 21,22 and was proposed to be a useful biomarker for prostate cancer.…”