Abstract
Abstract MicroRNAs (miRNAs) are key gene regulators in most biological and pathological processes, including colorectal cancer (CRC). The possibility of using circulating or fecal miRNA expression levels as non-invasive biomarkers open interesting possibilities for their potential clinical utility. Next-generation sequencing (NGS) technologies have changed the approach to complex genomic studies, including those on noncoding RNAs, providing a reliable and accurate method for grouping individuals on the basis of their molecular profiles. We report our study on the search of CRC biomarkers in surrogate specimens by a concomitant evaluation of miRNA expression profiles in plasma and stool samples from healthy subjects and patients with CRC or precancerous lesions. In particular, miRNA expression profiles were characterized by NGS (small RNA sequencing) in exosome isolated from plasma and in stool samples of a discovery set (n=130) of CRC/adenoma/inflammatory disease patients and healthy subjects recruited at colonoscopy. An optimized workflow for miRNAs quantification from NGS and an analysis pipeline has been developed for pre-processing the raw sequences, aligning the data to a known reference sequence and finally, analyzing the compiled sequence. Information on lifestyle and dietary habits were collected at the time of enrolment, together with biological samples. Preliminary results of a set of 96 plasma/stool samples showed that several miRNAs resulted dysregulated in all categories of subjects with disease in comparison with healthy subjects. In particular, in stool of CRC patients more than 140 miRNAs showed altered expression levels in comparison with healthy controls after adjusting for multiple testing. Among them, we have recorded miRNAs already observed in primary tissue, such as over-expressed miR-92a and miR-21, but also miRNAs previously not described. A group of eleven miRNAs showed similar trends between plasma and stool samples. The most relevant identified dysregulated miRNAs will be validated by qPCR in an additional group with similar distributions of cases/controls. The present study shows the importance to use high-throughput techniques and complex computational analyses to globally define miRNA signatures involved in colorectal carcinogenesis in surrogate specimens. Stool miRNAs analyzed by NGS for the first time in the present study seem to provide reliable and comparable results to other specimens (number of mapped sequences/identified miRNAs). Their future use in clinical practice may help to avoid unnecessary and expensive colonoscopies in low-risk patients. Citation Format: Alessio Naccarati, Sonia Tarallo, Gaetano Gallo, Giulio Ferrero, Antonio Francavilla, Giuseppe Clerico, Alberto Realis, Mario Trompetto, Francesca Cordero, Barbara Pardini, Paolo Vineis. Stool and plasma miRNA profiles by next-generation sequencing: a study on subjects with colorectal cancer and precancerous lesions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-330. doi:10.1158/1538-7445.AM2017-LB-330
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