Urinary prostate protein glycosylation profiling as a diagnostic biomarker for prostate cancer

Abstract

BACKGROUND: Serum prostate-specific antigen (sPSA) measurement is widely used as opportunistic screening tool for prostate cancer (PCa). sPSA suffers from considerable sensitivity and specificity problems, particularly in the diagnostic gray zone (sPSA 4-10 µg/L). Furthermore, sPSA is not able to discriminate between poorly-, moderately-, and well-differentiated PCa. We investigated prostatic protein glycosylation profiles as a potential PCa biomarker. METHODS: Differences in total urine N-glycosylation profile of prostatic proteins were determined between healthy volunteers (n = 54), patients with benign prostate hyperplasia (BPH; n = 93) and newly diagnosed PCa patients (n = 74). Variations in N-glycosylation profile and prostate volume were combined into one urinary glycoprofile marker (UGM). Additionally, differences in N-glycosylation were identified between Gleason <7, =7, and >7. RESULTS: The UGM was able to discriminate BPH from PCa, overall and in the diagnostic gray zone (P < 0.001). The UGM showed comparable diagnostic accuracy to sPSA, but gave an additive diagnostic value to sPSA (P < 0.001). In the diagnostic gray zone the UGM performed significantly better than sPSA (P < 0.001). A significant difference was found in core-fucosylation of biantennary structures and overall core-fucosylation of multiantennary structures between Gleason < 7 and Gleason > 7 (P = 0.010 and P = 0.020, respectively) and between Gleason = 7 and Gleason > 7 (P = 0.011 and P = 0.025, respectively). CONCLUSIONS: The UGM shows high potential as PCa biomarker, particularly in the diagnostic gray zone. Further research is needed to validate these findings.