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

Prostate. 2015 Feb 15;75(3):314-22. doi: 10.1002/pros.22918. Epub 2014 Oct 30.

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.

Keywords: Gleason score; benign prostate hyperplasia; diagnostic marker; prostate cancer; urinary asparagine-linked glycosylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / urine
  • Diagnosis, Differential
  • Glycosylation
  • Humans
  • Male
  • Middle Aged
  • Prostatic Hyperplasia / diagnosis*
  • Prostatic Hyperplasia / urine
  • Prostatic Neoplasms / diagnosis*
  • Prostatic Neoplasms / urine
  • Proteins / metabolism*
  • Sensitivity and Specificity
  • Young Adult

Substances

  • Biomarkers
  • Proteins