A specific miRNA signature correlates with complete pathological response to neoadjuvant chemo-radiotherapy in locally advanced rectal cancer

Purpose: MicroRNAs (miRNAs) are small, non-coding RNA molecules that can be down- or up-regulated in colorectal cancer and have been associated to prognosis and response to treatment. We studied miRNA expression in tumor biopsies of patients with rectal cancer to identify a specific “signature” correlating with pathological complete response (pCR) after neoadjuvant chemo-radiotherapy. Methods and Materials: 38 T3-4/N+ rectal cancer patients received capecitabine-oxaliplatin and radiotherapy followed by surgery. Pathologic response was scored according to the Mandard TRG scale. MiRNA expression was analysed by microarray and confirmed by RT-PCR on frozen biopsies obtained before treatment. The correlation between miRNA expression and TRG, coded as TRG1 (pCR) versus TRG >1 (no pCR), was assessed by methods specifically designed for this study. Results: Microarray analysis selected 14 miRNAs as being differentially expressed in TRG1 patients, and 13 were confirmed by RT-PCR: 11 miRNAs (miR-1183, miR-483-5p, miR-622, miR-125a-3p, miR-1224-5p, miR-188-5p, miR-1471, miR-671-5p, miR-1909*, miR-630, miR-765) were significantly up-regulated in TRG1 patients, 2 (miR-1274b, miR-720) were down-expressed. MiR-622 and miR-630 had a 100% sensitivity and specificity in selecting TRG1 cases. Conclusions: A set of 13 miRNAs is strongly associated with pCR and may represent a specific