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.
Highlights
Elevation of the prostate-specific antigen (PSA) level and/or an abnormal digital rectal examination (DRE) leads to prostate needle biopsy to diagnose prostate cancer
We performed shotgun proteomics of extracellular vesicles (EVs) in urine collected after prostate massage to identify potential biomarker candidates for Gleason score (GS) prostate cancer
The development of new biomarkers for high-risk prostate cancer is continuing by many researchers using various methods
Summary
Elevation of the prostate-specific antigen (PSA) level and/or an abnormal digital rectal examination (DRE) leads to prostate needle biopsy to diagnose prostate cancer. Needle biopsy Gleason grade is routinely used for guiding patient management decisions[2] It is controversial whether GS6 prostate cancer should be labeled as cancer because patients with GS6 prostate cancer have a similar prognosis with or without treatment[3]. Urine collected after prostate massage was reported to contain extracellular vesicles (EVs) that are secreted from prostate cancer cells[10,11]. Cancer-cell-derived EVs can be measured by two types of antibodies for CD9 and the biomarker protein in a high-throughput manner[22]. We performed quantitative proteomic analysis of EV proteins from urine collected after prostate massage to discover potential biomarker candidates for the diagnosis of high GS prostate cancer and verified the candidate proteins
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