title: Seminal plasma as a source of prostate cancer peptide biomarker candidates for detection of indolent and advanced disease.
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.
  
  
  RESULTS
  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
  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.
authors.affiliation: University of Leipzig, Department of Urology, Leipzig, Germany. jochen.neuhaus@medizin.uni-leipzig.de
authors.forename: Jochen
authors.initials: J
authors.lastname: Neuhaus
authors.forename: Eric
authors.initials: E
authors.lastname: Schiffer
authors.forename: Philine
authors.initials: P
authors.lastname: von Wilcke
authors.forename: Hartwig W
authors.initials: HW
authors.lastname: Bauer
authors.forename: Hing
authors.initials: H
authors.lastname: Leung
authors.forename: Justyna
authors.initials: J
authors.lastname: Siwy
authors.forename: Wolfram
authors.initials: W
authors.lastname: Ulrici
authors.forename: Uwe
authors.initials: U
authors.lastname: Paasch
authors.forename: Lars-Christian
authors.initials: LC
authors.lastname: Horn
authors.forename: Jens-Uwe
authors.initials: JU
authors.lastname: Stolzenburg
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D014408:Biomarkers, Tumor / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D020543:Proteome / Q000378:metabolism; D040901:Proteomics; D015203:Reproducibility of Results; D012661:Semen / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D010455:Peptides; D020543:Proteome