Proteomic analysis of urinary extracellular vesicles from high Gleason score prostate cancer

Sci Rep. 2017 Feb 17:7:42961. doi: 10.1038/srep42961.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Area Under Curve
  • Biomarkers, Tumor / urine
  • Chromatography, High Pressure Liquid
  • Extracellular Vesicles / metabolism*
  • Fatty Acid-Binding Proteins / metabolism
  • Fatty Acid-Binding Proteins / urine
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Prostatic Neoplasms / pathology*
  • Proteome / analysis*
  • Proteomics*
  • ROC Curve
  • Tandem Mass Spectrometry

Substances

  • Biomarkers, Tumor
  • FABP5 protein, human
  • Fatty Acid-Binding Proteins
  • Proteome