Abstract 299: Circulating microRNAs in association with colorectal neoplasia

Abstract

Abstract Purpose: MicroRNAs (miRNAs) are non-coding regulatory RNAs that are stable in circulation and implicated in the etiology of many cancers including colorectal cancer (CRC). In this study we investigated whether candidate miRNAs could serve as blood-based biomarkers of colorectal adenoma. Methods: We conducted a colonoscopy-based case-control study of men and women ages 50-79; this report includes data from 48 polyp-free controls, 43 advanced adenoma, 73 non-advanced adenomas, and 8 CRC cases. We selected 12 miRNA candidates that are highly expressed in adenoma tissue and have low expression in blood cells, in addition to miRNAs previously reported as biomarkers of adenoma. miRNAs were extracted from stored plasma samples, and copy number assessed with qRT-PCR. Odds ratios (ORs) and area-under-the-curve (AUC) from receiver-operator characteristic curves were estimated to quantify the association between plasma copy-number of these candidate miRNAs and each case group. Results: No miRNA transcripts were associated with risk of adenoma or advanced adenomas, or with an AUC significantly above 0.5 that would indicate usefulness in discriminating either category of adenoma cases from controls. In contrast, statistically significant and strong associations (ORs>5) with CRC were observed for 6 miRNA candidates, with corresponding AUCs significantly greater than 0.5. Conclusions: Our results suggest that these candidate miRNAs, assayed with qRT-PCR, are unlikely to have clinical utility as blood-based screening biomarkers of adenomas. However, strong associations were observed with CRC. Circulating miRNAs may therefore have promise as potential early detection biomarkers to augment current CRC screening methods, but an optimal screening biomarker would detect pre-malignant colorectal adenomas as well as frank CRC. Citation Format: Scott V. Adams, Polly A. Newcomb, Andrea N. Burnett-Hartman, Melissa P. Upton, Lee-Ching Zhu, Margaret Mandelson, John D. Potter, Karen W. Makar. Circulating microRNAs in association with colorectal neoplasia. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 299. doi:10.1158/1538-7445.AM2014-299