Abstract
BackgroundThe objective of this study was to discover and to validate novel noninvasive biomarkers that distinguish between benign prostate hyperplasia (BPH) and localized prostate cancer (PCa), thereby helping to solve the diagnostic dilemma confronting clinicians who treat these patients.MethodsQuantitative iTRAQ LC/LC/MS/MS analysis was used to identify proteins that are differentially expressed in the urine of men with BPH compared with those who have localized PCa. These proteins were validated in 173 urine samples from patients diagnosed with BPH (N = 83) and PCa (N = 90). Multivariate logistic regression analysis was used to identify the predictive biomarkers.ResultsThree proteins, β2M, PGA3, and MUC3 were identified by iTRAQ and validated by immunoblot analyses. Univariate analysis demonstrated significant elevations in urinary β2M (P < 0.001), PGA3 (P = 0.006), and MUC3 (P = 0.018) levels found in the urine of PCa patients. Multivariate logistic regression analysis revealed AUC values ranging from 0.618 for MUC3 (P = 0.009), 0.625 for PGA3 (P < 0.008), and 0.668 for β2M (P < 0.001). The combination of all three demonstrated an AUC of 0.710 (95% CI: 0.631 – 0.788, P < 0.001); diagnostic accuracy improved even more when these data were combined with PSA categories (AUC = 0.812, (95% CI: 0.740 – 0.885, P < 0.001).ConclusionsUrinary β2M, PGA3, and MUC3, when analyzed alone or when multiplexed with clinically defined categories of PSA, may be clinically useful in noninvasively resolving the dilemma of effectively discriminating between BPH and localized PCa.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1284-z) contains supplementary material, which is available to authorized users.
Highlights
The objective of this study was to discover and to validate novel noninvasive biomarkers that distinguish between benign prostate hyperplasia (BPH) and localized prostate cancer (PCa), thereby helping to solve the diagnostic dilemma confronting clinicians who treat these patients
Age-adjusted prostate-specific antigen (PSA) ranges, PSA velocity, PSA density, and free PSA fraction have all been disappointing in their ability to discriminate between BPH and prostate cancer [16], making it very difficult to differentiate between these two diseases in a clinical setting
25 proteins were differentially expressed in the urine of patients diagnosed with BPH vs. PCa as originally identified by iTRAQ (Figure 1)
Summary
The objective of this study was to discover and to validate novel noninvasive biomarkers that distinguish between benign prostate hyperplasia (BPH) and localized prostate cancer (PCa), thereby helping to solve the diagnostic dilemma confronting clinicians who treat these patients. The PSA test has been widely used as a diagnostic, screening, and monitoring tool since it was first approved by the US Food and Drug Administration in 1986 as an aid for the early detection of prostate cancer [9] This test lacks high sensitivity and specificity for PCa and PSA levels are frequently elevated in benign conditions, Jedinak et al BMC Cancer (2015) 15:259 including BPH [10]. For PSA levels between 4.1 to 10.0 ng/mL, the positive predictive value (PPV) for prostate cancer is 25% and, for PSA levels greater than 10 ng/mL, reported PPVs have ranged from 42 to 64% [12,13] This leads to a situation in which men with indolent disease or BPH continue to be overdiagnosed and unnecessarily biopsied [14]. In May of 2012, the United States Preventive Services Task Force (USPSTF) announced that PSA screening for prostate cancer demonstrated small potential benefit against a backdrop of potential harms [17], including misdiagnosis
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