title: Proteomic analysis of urinary extracellular vesicles from high Gleason score prostate cancer.
abstract: Extracellular vesicles (EVs) are microvesicles secreted from various cell types. We aimed to discover a new biomarker for high Gleason score (GS) prostate cancer (PCa) in urinary EVs via quantitative proteomics. 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. We identified 4710 proteins and quantified 3528 proteins in the urinary EVs. Eleven proteins increased in patients with PCa compared to those with negative biopsy (ratio >1.5, p-value < 0.05). Eleven 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). Granulin, AMBP, CHMP4A, and CHMP4C were also higher in men with high GS prostate cancer (p-value < 0.05). FABP5 in urinary EVs could be a potential biomarker of high GS PCa.
authors.affiliation: Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Fujita
authors.affiliation: Laboratory of Proteome Research, National Institute of Biomedical Innovation, Health and Nutrition, Osaka, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kume
authors.affiliation: Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Matsuzaki
authors.affiliation: Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Atsunari
authors.initials: A
authors.lastname: Kawashima
authors.affiliation: Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ujike
authors.affiliation: Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Nagahara
authors.affiliation: Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Motohide
authors.initials: M
authors.lastname: Uemura
authors.affiliation: Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Miyagawa
authors.affiliation: Laboratory of Proteome Research, National Institute of Biomedical Innovation, Health and Nutrition, Osaka, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tomonaga
authors.affiliation: Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Nonomura
mesh_terms: D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D000067128:Extracellular Vesicles / Q000378:metabolism*; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism / Q000652:urine; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011471:Prostatic Neoplasms / Q000473:pathology*; D020543:Proteome / Q000032:analysis*; D040901:Proteomics; D012372:ROC Curve; D053719:Tandem Mass Spectrometry
chemical_list: D014408:Biomarkers, Tumor; C493412:FABP5 protein, human; D050556:Fatty Acid-Binding Proteins; D020543:Proteome