Seminal plasma as a source of prostate cancer peptide biomarker candidates for detection of indolent and advanced disease

PLoS One. 2013 Jun 24;8(6):e67514. doi: 10.1371/journal.pone.0067514. Print 2013.

Abstract

Background: Extensive prostate specific antigen screening for prostate cancer generates a high number of unnecessary biopsies and over-treatment due to insufficient differentiation between indolent and aggressive tumours. We hypothesized that seminal plasma is a robust source of novel prostate cancer (PCa) biomarkers with the potential to improve primary diagnosis of and to distinguish advanced from indolent disease.

Methodology/principal findings: In an open-label case/control study 125 patients (70 PCa, 21 benign prostate hyperplasia, 25 chronic prostatitis, 9 healthy controls) were enrolled in 3 centres. Biomarker panels a) for PCa diagnosis (comparison of PCa patients versus benign controls) and b) for advanced disease (comparison of patients with post surgery Gleason score <7 versus Gleason score >7) were sought. Independent cohorts were used for proteomic biomarker discovery and testing the performance of the identified biomarker profiles. Seminal plasma was profiled using capillary electrophoresis mass spectrometry. Pre-analytical stability and analytical precision of the proteome analysis were determined. Support vector machine learning was used for classification. Stepwise application of two biomarker signatures with 21 and 5 biomarkers provided 83% sensitivity and 67% specificity for PCa detection in a test set of samples. A panel of 11 biomarkers for advanced disease discriminated between patients with Gleason score 7 and organ-confined (<pT3a) or advanced (≥pT3a) disease with 80% sensitivity and 82% specificity in a preliminary validation setting. Seminal profiles showed excellent pre-analytical stability. Eight biomarkers were identified as fragments of N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase, prostatic acid phosphatase, stabilin-2, GTPase IMAP family member 6, semenogelin-1 and -2. Restricted sample size was the major limitation of the study.

Conclusions/significance: Seminal plasma represents a robust source of potential peptide makers for primary PCa diagnosis. Our findings warrant further prospective validation to confirm the diagnostic potential of identified seminal biomarker candidates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Biomarkers, Tumor / chemistry
  • Biomarkers, Tumor / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Neoplasm Staging
  • Peptides / chemistry
  • Peptides / metabolism*
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology*
  • Proteome / metabolism
  • Proteomics
  • Reproducibility of Results
  • Semen / metabolism*
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • Peptides
  • Proteome

Grant support

This study was funded in part by the German Ministry of Economy and Technolgy BMWi with grant No. KF0362802MD8 to JUS, JN, PW, ES, JS and grant No. EP110141 to ES and JS. No additional external funding was received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.