Potential Marker for Response to Anti-EGFR Therapy in KRAS Wild-Type Metastatic Colorectal Cancer

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As reported in Clinical Cancer Research, Manceau and colleagues attempted to identify microRNAs that can predict response to anti-EGFR therapy in wild-type KRAS metastatic colorectal cancer patients.

Initial screening of 1,145 microRNAs in fresh frozen tumor samples from chemotherapy-refractory metastatic colorectal cancer patients who were treated with anti-EGFR therapy showed a significant association between has-miR-131-3p expression and progression-free survival. Studies in vitro identified a total of 47 genes regulated by hsa-miR-31-3p. Statistical models based on has-miR-131-3p expression discriminated high vs low risk of progression in both fresh frozen and formalin-fixed paraffin embedded (FFPE) samples.

The models were confirmed in a validation cohort for both fresh frozen (hazard ratio [HR] = 4.1, P < .04) and FFPE samples (HR = 2.44, P = .028). The percentage of variation in RECIST responses in the validation cohort was significantly associated with both level of hsa-miR-31-3p expression (r2 = 0.49, P = .0035) and risk status based on expression level (P = .02). The investigators constructed and validated nomograms to predict progression-free survival based on hsa-miR-31-3p expression level.

The investigators concluded, “Hsa-miR-31-3p appears to be a new [metastatic colorectal cancer] biomarker whose expression level allows for the identification of patients with wild-type KRAS [metastatic colorectal cancer] who are more likely to respond to anti-EGFR therapy.” ■

Manceau G, et al: Clin Cancer Res 20:3338-3347, 2014.