Untargeted multi-omic analysis of colorectal cancer-specific exosomes reveals joint pathways of colorectal cancer in both clinical samples and cell culture. (28th January 2020)

• Record Type: Journal Article
• Authors: Eylem, Cemil Can; Yilmaz, Mehmet; Derkus, Burak; Nemutlu, Emirhan; Camci, Can Berk; Yilmaz, Erkan; Turkoglu, Mehmet Akif; Aytac, Bulent; Ozyurt, Neslihan; Emregul, Emel
• Is Part Of: Cancer letters. Volume 469(2020)
• Page Start: 186
• Page End: 194
• Publication Date: 2020-01-28
• Subjects: Exosome -- Proteomics -- Metabolomics -- miRNA -- Colorectal cancer; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2019.10.038
• Languages: English
• ISSNs: 0304-3835

Abstract

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. Graphical abstract: Image 1 Highlights: CRC derived exosomes are suitable candidates for discriminating CRC from healthy control. MiR19a, miR21, miR92a and miR1246 positive exosomes reflect the metabolic, proteomic and lipidomic structure of CRC. Serum-derived and cell culture-derived exosomes indicate various common pathways. Exosomes can be utilized as non-invasive diagnostic tools for CRC diagnosis.