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

Neuhaus, J., Schiffer, E., von Wilcke, P., Bauer, H.W., Leung, H., Siwy, J., Ulrici, W., Paasch, U., Horn, L.C. and Stolzenburg, J.U. (2013) Seminal plasma as a source of prostate cancer peptide biomarker candidates for detection of indolent and advanced disease. PLoS ONE, 8(6), e67514. (doi: 10.1371/journal.pone.0067514) (PMID:23826311) (PMCID:PMC3691205)

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. <br>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.</br> <br>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.</br>

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Leung, Professor Hing and Schiffer, Dr Eric
• Authors: Neuhaus, J., Schiffer, E., von Wilcke, P., Bauer, H.W., Leung, H., Siwy, J., Ulrici, W., Paasch, U., Horn, L.C., and Stolzenburg, J.U.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences; College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: PLoS ONE
• Publisher: Public Library of Science
• ISSN: 1932-6203
• ISSN (Online): 1932-6203
• Copyright Holders: Copyright © 2013 The Authors
• First Published: First Published in PLoS One 8(6):e67514
• Publisher Policy: Reproduced under a Creative Commons License