MP99-01 PROTEOMIC ANALYSIS OF URINARY EXTRACELLULAR VESICLES FROM HIGH GLEASON SCORE PROSTATE CANCER

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology IV1 Apr 2017MP99-01 PROTEOMIC ANALYSIS OF URINARY EXTRACELLULAR VESICLES FROM HIGH GLEASON SCORE PROSTATE CANCER Kazutoshi Fujita, Hideaki Kume, Kyosuke Matsuzaki, Atsunari Kawashima, Takeshi Ujike, Akira Nagahara, Motohide Uemura, Yasushi Miyagawa, Takeshi Tomonaga, and Norio Nonomura Kazutoshi FujitaKazutoshi Fujita More articles by this author , Hideaki KumeHideaki Kume More articles by this author , Kyosuke MatsuzakiKyosuke Matsuzaki More articles by this author , Atsunari KawashimaAtsunari Kawashima More articles by this author , Takeshi UjikeTakeshi Ujike More articles by this author , Akira NagaharaAkira Nagahara More articles by this author , Motohide UemuraMotohide Uemura More articles by this author , Yasushi MiyagawaYasushi Miyagawa More articles by this author , Takeshi TomonagaTakeshi Tomonaga More articles by this author , and Norio NonomuraNorio Nonomura More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.3087AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Extracellular vesicles (EVs) are microvesicles secreted from various cell types. EVs contain microRNAs, proteins, and mRNAs and play a role in intercellular communications via the mechanisms of exocytosis and endocytosis. We aimed to discover a new biomarker for high Gleason score (GS) prostate cancer (PCa) in urinary EVs via quantitative proteomics. METHODS EVs were isolated from urine after massage from 18 men (negative biopsy [n = 6], GS 6 PCa [n = 6], or GS 8-9 PCa [n = 6]). EV proteins were labeled with iTRAQ and analyzed by LC-MS/MS. Candidate proteins were further analyzed by selected reaction monitoring/multiple reaction monitoring (SRM/MRM). RESULTS Proteins extracted from EVs were enriched with CD9 protein, which is a marker of EVs, compared with unprocessed urinary proteins. EVs labeled with anti-CD9 antibody conjugated with Au colloids were also confirmed by electron microscopy. We identified and quantified 3530 proteins in the urinary EVs by LC-MS/MS. Thirty-six proteins increased in patients with PCa compared to those with negative biopsy (ratio > 2.0, p < 0.1). Four proteins increased in patients with GS 8-9 PCa compared to those with negative biopsy or GS 6 PCa (ratio > 2.0, p < 0.1). Twenty-seven proteins were chosen for further analysis and verified in 29 independent urine samples (negative [n = 11], PCa [n = 18]) using SRM/MRM. Among these candidate markers, fatty acid binding protein 5 (FABP5) was higher in the cancer group than in the negative group (p = 0.009) and was significantly associated with GS (p for trend = 0.011). Univariate logistic analysis showed that FABP5 was significantly associated with prostate cancers with GS 7 or more (p < 0.001). Even after adjusting for age, PSA, and PSA density, FABP5 was significantly associated with prostate cancer with GS 7 or more (p = 0.003). The receiver-operator characteristics curve analysis showed that the area under the curve (AUC) for the prediction of GS = 7 by FABP5 was 0.856 (95% CI 0.708–1.00, p = 0.002), whereas the AUC value for prediction by serum PSA was 0.511 (95% CI 0.280–0.757, p = 0.87). CONCLUSIONS We applied the proteomic analysis to discover biomarkers in EVs in urine collected after prostate massage. FABP5 in urinary EVs could be a potential biomarker of high GS prostate cancer. Additional large-scale studies are warranted to confirm this finding. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1320 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Kazutoshi Fujita More articles by this author Hideaki Kume More articles by this author Kyosuke Matsuzaki More articles by this author Atsunari Kawashima More articles by this author Takeshi Ujike More articles by this author Akira Nagahara More articles by this author Motohide Uemura More articles by this author Yasushi Miyagawa More articles by this author Takeshi Tomonaga More articles by this author Norio Nonomura More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...