Untargeted multi-omic analysis of colorectal cancer-specific exosomes reveals joint pathways of colorectal cancer in both clinical samples and cell culture

Cancer Lett. 2020 Jan 28:469:186-194. doi: 10.1016/j.canlet.2019.10.038. Epub 2019 Oct 25.

Abstract

Exosomes are naturally secreted nano-vesicles consisting of biochemical molecules including RNAs, metabolites, lipids, and proteins, that emerge as diagnostic tools and disease-specific reporters. Here we offer a systematic and integrative approach for the simultaneous analysis of altered molecules namely metabolites, lipids, and proteins. These components tend to augment the discovery of low abundance signature components, and assist in explanation of molecular basis of colorectal cancer (CRC). In order to investigate CRC-derived exosomes, we selected mi-R19a, miR-21, miR-92a, and miR-1246 positive exosomes for downstream experiments. The overall multi-omic changes were investigated comparatively in cell culture and serum samples. Following a systematic multi-omic study, 37 (cell culture) and 31 (serum) metabolites; 130 (cell culture) and 56 (serum) lipids; 9 (cell culture) and 13 (serum) proteins were seen to be differentially expressed (p < 0.05), enabling discrimination between CRC and control. By using these enriched components, we demonstrated that the joint pathways mainly involving fatty acid and amino acid metabolism related pathways changed in CRC significantly. We conclude that this study increases our understanding of molecular basis of CRC, and provides potential exosomal biomarkers for the non-invasive detection, and discrimination of CRC.

Keywords: Colorectal cancer; Exosome; Metabolomics; Proteomics; miRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amino Acids / metabolism
  • Biomarkers, Tumor / metabolism*
  • Cell Line, Tumor
  • Colorectal Neoplasms / blood
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Exosomes / genetics
  • Exosomes / metabolism*
  • Fatty Acids / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lipidomics
  • Liquid Biopsy
  • Male
  • Metabolic Networks and Pathways / genetics*
  • MicroRNAs / metabolism*
  • Middle Aged
  • Proteomics

Substances

  • Amino Acids
  • Biomarkers, Tumor
  • Fatty Acids
  • MicroRNAs