Abstract 3432: microRNA expression reflects site specificity of metastatic colorectal cancer

Abstract

Abstract Colorectal Cancer (CRC) is one of the leading causes of cancer related deaths in the western world, and metastatic progression is the dominating cause of mortality. The primary site of CRC metastasis is the liver, followed by the lungs and peritoneal cavity, and prognosis for patients with metastatic CRC (mCRC) is poor, with only 10 % five-year survival. Although much is known about progression and metastasis of CRC; how primary CRC (pCRC) differs from mCRC on the molecular level and potential differences between metastases located in different organs are incompletely understood. This is important for our understanding of the disease, but also could have significant implications with respect to treatment. MicroRNAs have been shown to be key elements in cancer progression, but recent reports on CRC failed to consistently identify microRNA signatures of metastatic progression. We have addressed this using a smallRNA sequencing approach to analyze primary tumors and a set of liver, lung and peritoneal metastases, including corresponding adjacent tissue (colon, liver, lung, peritoneum). Further, we use the highly curated and updated microRNA reference MirGeneDB.org, the novel pipeline MirAthon - including a correction-algorithm of benign tissue microRNA signatures for tumor or metastatic samples, and we compare pCRC and site specific metastases separately. We are able to show that microRNA profiles of mCRC are distinct to pCRC in a site-specific manner. We identify a small panel of differentially expressed microRNAs including isoforms (isomiRs) hidden under a layer of benign signatures that we confirmed in other available datasets, too. Our findings will help better understand metastatic progression and site-specificity in CRC and could be potential biomarkers for mCRC. Our work identifies microRNA signatures of mCRC and suggest that microRNA signatures reflect mCRC site specificity. Furthermore, the results underline the importance of using a curated reference for microRNA studies, and to differentiate metastases based on their localization ab initio. Citation Format: Bastian Fromm, Eirik Høye, Diana Domanska, Christin Lund-Andersen, Annette Torgrund Kristensen, Vegar J. Dagenborg, Paul H. Boettger, Torveig W. Abrahamsen, Steinar Solberg, Stein G. Larsen, Bjørn Edwin, Eivind Hovig, Susanne Lorenz, Kjersti Flatmark. microRNA expression reflects site specificity of metastatic colorectal cancer [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 3432. doi:10.1158/1538-7445.AM2017-3432