Abstract 6446: Liquid biopsy in colon cancer utilizing exosomal miRNA biomarkers: An initial analysis

Abstract

Abstract Traditional clinicopathologic variables do not predict recurrence and disease progression in colorectal cancer (CRC) accurately. Development of a liquid biopsy as a means to obtain real-time, clinically meaningful biomarkers to assess progression and response to treatment is critical. Current liquid biopsy techniques utilizing circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) have significant limitations. Exosomes are emerging as a promising tool for liquid biopsy due to their stability and role in cancer cell to cell communication. To that end, the purpose of this study is to describe patterns of highly abundant microRNA (miRNA) found in serum exosomes of patients with metastatic colon cancer as a step toward developing an exosomal miRNA signature for liquid biopsy. Next generation sequencing was performed on exosomes isolated from serum of stage IV colon cancer patients (n=9) to determine the miRNA read counts. miRNA data from primary tumors (n=53) of stage IV colon cancer patients and available paired peritumoral tissue (n=8) were obtained from The Cancer Genome Atlas (TCGA) database for qualitative comparison. There were 515 total miRNA shared in common between the serum exosomes and primary tumors and 277 miRNA uniquely present in serum exosomes. In our initial analysis, we identified five miRNA, two in the common pool (mir-486-1 and mir-486-2) and three in the unique group (miR-486-5p, miR-92a-3p, and miR-146a-5p) that were most abundant in serum exosomes and may serve as biomarkers. mir-486-1 and mir-486-2 were the most highly abundant miRNAs in exosomes, but were only expressed at low levels in the tissue. This inverse relationship has been demonstrated by other investigators, with decreased levels of tissue mir-486 associated with more advanced stages of disease and poorer survival. Exosomal miR-92a-3p has been shown to correlate with tumor grade and stage in CRC patients. Delivery of miR-146a-5p by exosomes has been shown to promote tumorigenesis and generate immunosuppressive microenvironment in CRC. In general, the top 10 most abundant exosomal miRNA were not among the most abundant tissue level miRNAs. Our group is currently analyzing the differential expression of serum exosomal miRNA from 52 additional patients with non-metastatic colon cancer (n=14), liver metastases (n=16) and PC (n=12) in comparison to healthy volunteer serum (n=10) to better characterize miRNA patterns at different stages of disease. In summary, highly abundant miRNA found in serum exosomes of patients with metastatic colon cancer demonstrate a different pattern of expression than miRNA found in the primary colon cancer itself. Further analysis of these miRNA patterns from serum exosomes of colon cancer patients with non-metastatic disease, visceral metastases and PC compared to normal volunteers will aid in the development of a serum exosomal miRNA signature. Citation Format: Audrey H. Choi, Paul A. Vallejos, Mei Li M. Kwong, Janviere Kabagwira, Matthew J. Selleck, Nathan R. Wall, Maheswari Senthil. Liquid biopsy in colon cancer utilizing exosomal miRNA biomarkers: An initial analysis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6446.