Identification of prostate-enriched proteins by in-depth proteomic analyses of expressed prostatic secretions in urine

Riccardo Alessandro, Simona Fontana, Vladimir Ignatchenko, Simona Principe, Raymond S. Lance, Yunee Kim, Thomas Kislinger, O. John Semmes, Simona Fontana, Jeffrey A. Medin, Dean A. Troyer, Richard R. Drake, Julius O. Nyalwidhe

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)

Abstract

Urinary expressed prostatic secretion or “EPS-urine” is proximal tissue fluidthat is collected after a digital rectal exam (DRE). EPS-urine is a rich source of prostatederived proteins that can be used for biomarker discovery for prostate cancer (PCa) and other prostatic diseases. We previously conducted a comprehensive proteome analysis of direct expressed prostatic secretions (EPS). In the current study, we defined the proteome of EPS-urine employing Multidimensional Protein Identification Technology (MudPIT) andproviding a comprehensive catalogue of this body fluid for future biomarker studies. Weidentified 1022 unique proteins in a heterogeneous cohort of 11 EPS-urines derived from biopsy negative noncancer diagnoses with some benign prostatic diseases (BPH) and lowgrade PCa, representative of secreted prostate and immune system-derived proteins in aurine background. We further applied MudPIT-based proteomics to generate and comparethe differential proteome from a subset of pooled urines (pre-DRE) and EPS-urines (post-DRE) from noncancer and PCa patients. The direct proteomic comparison of these highlycontrolled patient sample pools enabled us to define a list of prostate-enriched proteins detectable in EPS-urine anddistinguishable from a complex urine protein background. A combinatorial analysis of both proteomics data sets and systematicintegration with publicly available proteomics data of related body fluids, human tissue transcriptomic data, and immunohistochemistry images from the Human Protein Atlas database allowed us to demarcate a robust panel of 49 prostate-derived proteins in EPS-urine. Finally, we validated the expression of seven of these proteins using Western blotting, supporting the likelihood that they originate from the prostate. The definition of these prostatic proteins in EPS-urine samples provides areference for future investigations for prostatic-disease biomarker studies.
Original languageEnglish
Pages (from-to)2386-2396
Number of pages11
JournalJournal of Proteome Research
Volume11
Publication statusPublished - 2012

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • General Chemistry

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