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)

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Publisher's URL: http://dx.doi.org/10.1371/journal.pone.0067514

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 > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN: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

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