1 Molecular Disease Biology, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, Københavns Universitet2 Molekylær medicinsk afdeling (MOMA)3 Section of Pathobiology, Department of Veterinary Disease Biology, Faculty of Life Sciences, Københavns Universitet4 Onkologi5 Institut for Eksperimentel Patologi6 Klinisk Patologi, Laboratoriecentret7 Onkologisk Afdeling D, NBG8 Herlev Hospital9 Vejle Hospital10 Section of Pathobiology, Department of Veterinary Disease Biology, Faculty of Life Sciences, Københavns Universitet11 Molecular Disease Biology, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, Københavns Universitet
The backbone of current cytotoxic treatment of metastatic colorectal cancer (mCRC) consists of a 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 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 94 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 [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 were up-regulated in oxaliplatin resistant HCT116/oxPt (miR-625-3p, miR-181b and miR-27b) and LoVo/oxPt (miR-181b) colon cancer 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.
Molecular Oncology, 2013, Vol 7, Issue 3, p. 637-646