MicroRNA Signature in Metastatic Colorectal Cancer Patients Treated With Anti-EGFR Monoclonal Antibodies

Abstract

BackgroundTo investigate whether microRNAs are predictive of sensitivity to anti–epidermal growth factor receptor (EGFR) monoclonal antibodies in patients with metastatic colorectal cancer (mCRC). MethodsA total of 183 mCRC cases from 2 independent cohorts (cohort 1: 74 cases; validation cohort: 109 cases) treated with cetuximab or panitumumab were included in the study. MiRNA arrays were analyzed using Agilent's miRNA platform. ResultsThe study identified the cluster Let-7c/miR-99a/miR-125b as a signature associated with an outcome different from that of anti-EGFR therapies. In the first cohort, patients with high-intensity signatures had a significantly longer progression-free survival (PFS) (6.1 vs. 2.3 mo; P = .02) and longer overall survival (OS) ( 29.8 vs. 7.0 mo, P = .08) than patients with low-intensity signatures. In the validation cohort, patients with high signature had significantly longer PFS and OS than individuals with low-intensity signatures (PFS 7.8 vs. 4.3 mo, P = .02; OS 12.8 vs. 7.5 mo, P = .02). In the KRAS wild-type population (n = 120), high-intensity signature patients had a significantly longer PFS (7.8 vs. 4.6 mo, P = .016) and longer OS (16.1 vs. 10.9 mo, P = .09) than low-signature individuals, with no difference in KRAS mutated patients. ConclusionThe MiR-99a/Let-7c/miR-125b signature may improve the selection of patients with KRAS wild-type mCRC as good candidates for anti-EGFR therapy.