EV-associated miRNAs from peritoneal lavage as potential diagnostic biomarkers in colorectal cancer

J Transl Med. 2019 Jun 20;17(1):208. doi: 10.1186/s12967-019-1954-8.

Abstract

Background: Colorectal cancer (CRC) is the third leading cause of cancer-related mortality worldwide. Current systematic methods for diagnosing have inherent limitations so development of a minimally-invasive diagnosis, based on the identification of sensitive biomarkers in liquid biopsies could therefore facilitate screening among population at risk.

Methods: In this study, we aim to develop a novel approach to identify highly sensitive and specific biomarkers by investigating the use of extracellular vesicles (EVs) isolated from the peritoneal lavage as a source of potential miRNA diagnostic biomarkers. We isolated EVs by ultracentrifugation from 25 ascitic fluids and 25 peritoneal lavages from non-cancer and CRC patients, respectively. Analysis of the expression of EV-associated miRNAs was performed using Taqman OpenArray technology through which we could detect 371 miRNAs.

Results: 210 miRNAs were significantly dysregulated (adjusted p value < 0.05 and abs(logFC) ≥ 1). The top-10 miRNAs, which had the AUC value higher than 0.95, were miRNA-199b-5p, miRNA-150-5p, miRNA-29c-5p, miRNA-218-5p, miRNA-99a-3p, miRNA-383-5p, miRNA-199a-3p, miRNA-193a-5p, miRNA-10b-5p and miRNA-181c-5p.

Conclusions: This finding opens the avenue to the use of EV-associated miRNA of peritoneal lavages as an untapped source of biomarkers for CRC.

Keywords: Ascitic fluid; Biomarkers; Colon cancer; Colorectal cancer; Diagnostic; Extracellular vesicles; Liquid biopsy; Peritoneal lavage; miRNAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / diagnosis*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Aged
  • Aged, 80 and over
  • Ascitic Fluid / metabolism*
  • Ascitic Fluid / pathology
  • Biomarkers, Tumor* / genetics
  • Biomarkers, Tumor* / metabolism
  • Case-Control Studies
  • Cohort Studies
  • Colorectal Neoplasms / diagnosis*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Extracellular Vesicles / genetics*
  • Extracellular Vesicles / metabolism
  • Female
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Peritoneal Lavage
  • Prognosis

Substances

  • Biomarkers, Tumor
  • MicroRNAs