Abstract 1157: MicroRNA-625-3p is associated with response to first-line oxaliplatin-based treatment of metastatic colorectal cancer.

The backbone of current oncologic treatment of metastatic colorectal cancer (mCRC) consists of fluoropyrimidine together with either oxaliplatin (XELOX/FOLFOX) or irinotecan (XELIRI/FOLFIRI). With an overall objective response rate of approximately 50% for either treatment combination, a major unsolved problem is that no predictors of response to these treatments currently are available. To address this issue, we profiled 742 microRNAs in laser-capture microdissected cancer cells from responding and non-responding patients receiving XELOX/FOLFOX as first-line treatment for mCRC, and identified, among others, high expression of miR-625-3p, miR-181b and miR-27b to be associated with poor clinical response. In a validation cohort of 98 mCRC patients treated first-line with XELOX, high expression of miR-625-3p was confirmed to be associated with poor response (OR 6.25, 95%CI OR [1.8; 21.0]). Independent analyses showed that miR-625-3p was not dysregulated between normal and cancer samples, nor was its expression associated with recurrence of stage II or III disease, indicating that miR-625-3p solely is a response marker. Finally, we also found that these miRNAs are up-regulated in oxaliplatin resistant HCT116/oxPt (miR-625-3p, miR-181b and miR-27b) and LoVo/oxPt (miR-181b) CRC cell lines as compared with their isogenic parental cells. Altogether, our results suggest an association between miR-625-3p and response to first-line oxaliplatin based chemotherapy of mCRC. Citation Format: Mads H. Rasmussen, Niels F. Jensen, Line S. Tarpgaard, Camilla Qvortrup, Maria U. Romer, Jan Stenvang, Tine P. Hansen, Lise-Lotte Christensen, Jan Lindebjerg, Flemming Hansen, Benny V. Jensen, Torben F. Hansen, Anders M. Jakobsen, Per Pfeiffer, Nils Brunner, Torben F. Orntoft, Claus L. Andersen. MicroRNA-625-3p is associated with response to first-line oxaliplatin-based treatment of metastatic colorectal cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1157. doi:10.1158/1538-7445.AM2013-1157