PDF file - 62KB, Kaplan-Meier PFS according to level of expression of hsa-miR-31-3p in the whole series of 132 patients. For the 102 patients who were NRAS wild-type based on Sanger sequencing of exon 2 and 3, the hazard ratio was 2.51 CI95 percent (1.6-4) and the median progression free survival was 10.14 and 35.71 weeks respectively for the high and low risk groups.
ARTICLE ABSTRACT
Purpose: To identify microRNAs (miRNA) that predict response to anti-EGFR antibodies in patients with wild-type KRAS metastatic colorectal cancer (mCRC).Experimental Design: miRNA profiling was performed in a training set of 87 patients with mCRC refractory to chemotherapy treated with anti-EGFR antibodies. This included 33 fresh-frozen (FF) and 35 formalin-fixed paraffin-embedded (FFPE) samples retrospectively collected and 19 prospectively collected FF samples. An independent validation cohort consisting of 19 FF and 26 FFPE prospectively collected samples from patients with mCRC treated with anti-EGFR antibodies was used to confirm our findings.Results: After screening the expression of 1,145 miRNAs in FF samples from the training set, we identified that hsa-miR-31-3p expression level was significantly associated with progression-free survival (PFS). Statistical models based on miRNA expression discriminated between high and low risk of progression for both FF and FFPE samples. These models were confirmed in the validation cohort for both FF [HR, 4.1; 95% confidence interval (CI), 1.1–15.3; P < 0.04] and FFPE samples (HR, 2.44; 95% CI, 1.1–5.4; P = 0.028). The percentage of variation of RECIST criteria in the validation series was significantly associated with the expression level of hsa-miR-31-3p (r2 = 0.49; P = 0.0035) and risk status determined by hsa-miR-31-3p expression level (P = 0.02, Kruskal–Wallis rank test). Nomograms were built and validated to predict PFS-depending on hsa-miR-31-3p expression level. Following in vitro studies, we identified 47 genes regulated by hsa-miR-31-3p.Conclusion: Hsa-miR-31-3p seems to be a new mCRC biomarker whose expression level allows for the identification of patients with wild-type KRAS mCRC who are more likely to respond to anti-EGFR therapy. Clin Cancer Res; 20(12); 3338–47. ©2014 AACR.
