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Hsa-miR-31-3p expression in FFPE tumor samples as a predictor of anti-EGFR response in patients with metastatic colorectal cancer.
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
Background: In metastatic colorectal cancer (mCRC), KRAS mutations are associated with resistance to anti-EGFR antibodies. To identify, in wild-type KRAS mCRC patients, markers that predict response to anti-EGFR antibodies, we focused on miRNAs. Methods: Expression profile of 1145 miRNAs was done on 84 colorectal tumors and 5 normal colon mucosae. Correlations between miRNAs expression level and survival were based on frozen samples of a training set from a retrospective series of 33 patients treated by cetuximab and irinotecan and of two validation set from prospective collections of 38 patients treated by cetuximab or panitumumab based chemotherapy or by panitumumab and irinotecan as third-line, using an adjusted Cox proportional hazards model. Validation on FFPE samples was done on 39 patients treated with panitumumab and irinotecan as third-line. Results: A predictive signature of 11 miRNA linked to the PFS was identified (p<0.01) but only one, hsa-miR-31-3p, exhibited significant different expression level between tumor from bad prognosis and good prognosis from the training set. We tested expression of this miRNA on the training set, and found a HR of 1.9 CI95% [1.1-2.9]. In validation set, the prognostic impact of hsa-miR-31-3p the HR was estimated to 1.9 CI95% [1.1-3.1]. Using multivariate model obtained from the training set to the two validation set, we predict the PFS of the patients (accuracy of prediction: AUC = 0.77). We classified the validation set according to a free PFS score (P=0.005) with a specificity of 62% CI95% [38%-82%] and a sensitivity of 82% CI95% [56%-96%] for the prediction model. A nomogram, established taking into account hsa-miR-31-3p expression level, predicted the progression risk (P<0.0001). Confirmation of the predictive value of hsa-miR-31-3p expression on survival risk progression was done on FFPE sample (p=0.0006). Conclusions: This is the first tool to select individual patients with a wild-type KRAS tumor for anti-EGFR therapy from frozen or FFPE samples.