High circulating miR-1247 is a marker for poor prognosis in patients with metastatic colorectal cancer treated with chemotherapy and cetuximab

Abstract

Abstract Background MicroRNAs (miRs) are small non-coding RNAs. Circulating miRs in plasma are deregulated in patients with metastatic colorectal cancer (mCRC). The aim was to find prognostic circulating miRs for overall survival (OS) in patients with mCRC treated with chemotherapy and cetuximab. Methods A prospective biomarker study was conducted. A full plasma miR-panel was tested with TaqMan Human MicroRNA assay in 151 patients treated with 3rd line irinotecan and cetuximab (Discovery cohort, Biweekly study). Significant miRs were validated with Fluidigm arrays, in 95 patients, treated with 1st line chemotherapy and cetuximab (Validation cohort, NORDIC-7.5 study1). Cox regression analysis was conducted, and multivariate analyses performed with adjustment for sidedness, number of metastatic sites, RAS/BRAF mutation status, age and performance status. Consecutive samples after 3 months of treatment were available for 117 and 86 patients in the discovery and validation cohorts, respectively. Results Baseline high expression of miR-1247 in the discovery and validation cohorts, was significantly associated with short OS (hazard ratio [HR]) = 2.33, p\xa0=\xa00.0005) based on the multivariate analysis in the validation cohort. High miR-1290 expression after 3 months was prognostic for short progression free-survival (HR\xa0=\xa01.57, p\xa0=\xa00.0465) in both cohorts. In both cohorts, we found a statistically significant decrease in, miR-1290 (p\xa0=\xa00.0051), miR-200b (p\xa0=\xa00.036), and miR-375 (p\xa0=\xa00.00005), from baseline to 3 month-sample, in patients with partial/complete (n\xa0=\xa078) response compared to patients with progressive disease (n\xa0=\xa072). Conclusions High expression of miR-1247 was prognostic for short OS in the multivariate analysis in a discovery and validation cohort of patients treated with chemotherapy and cetuximab in both first and third line. A decrease in miR-1247 and miR-1290 during treatment was associated with favorable response. 1Pfeiffer et al, Clin Colorectal Cancer 2015. Legal entity responsible for the study Jakob Vasehus Scho. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.