Abstract 2202: FABP5 in urinary extracellular vesicles is a potential biomarker of high Gleason score prostate cancer

Abstract

Abstract Urine collected after prostate massage is a promising source of new biomarkers of prostate cancer, and was reported to contain extracellular vesicles (EVs) that are secreted from prostate cancer cells. 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. Material and methods: Urine samples after massage were collected from 18 patients before prostate needle biopsy. Six patients had negative biopsy outcomes, 6 had Gleason score 6 prostate cancer (GS6), and 6 had Gleason score 8 to 9 prostate cancer (GS8-9). Urinary EVs were isolated from urine with ultracentrifuge. Protein extracted from EVs were labeled with 4-plex iTRAQ and liquid chromatography tandem mass spectrometry (LC-MS/MS) was used for proteome analysis. The candidate proteins were quantitated in the independent set by selected reaction monitoring/multiple reaction monitoring analysis (SRM/MRM). Results: Seven proteins increased in patients with PCa compared to those with negative biopsy (ratio > 2.0, p-value < 0.05). Thirteen proteins were chosen for further analysis and verified in 29 independent urine samples (negative [n = 11], PCa [n = 18]) using selected reaction monitoring/multiple reaction monitoring. Among these candidate markers, fatty acid binding protein 5 (FABP5) was higher in the cancer group than in the negative group (p-value = 0.009) and was significantly associated with GS (p-value for trend = 0.011). 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. Citation Format: Kazutoshi Fujita, Hideaki Kume, Kyosuke Matsuzaki, Atsunari Kawashima, Takeshi Ujike, Akira Nagahara, Motohide Uemura, Yasushi Miyagawa, Takeshi Tomonaga, Norio Nonomura. FABP5 in urinary extracellular vesicles is a potential biomarker of high Gleason score prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2202. doi:10.1158/1538-7445.AM2017-2202