hERG1 and HIF-2α Behave as Biomarkers of Positive Response to Bevacizumab in Metastatic Colorectal Cancer Patients

Background: In search of novel biomarkers of response to Bevacizumab in metastatic colorectal cancer (mCRC), we analysed the expression and prognostic role of several proteins related to angiogenesis. Methods: A retrospective, multicenter study on 80 surgical samples from mCRC patients treated in first line with Bevacizumab plus chemotherapy was accomplished. The following proteins were analysed by immunohistochemistry: hERG1 potassium channel, β1-integrin, pAKT, NFkB, HIF-1α, HIF-2α, p53, VEGF-A, GLUT-1 and CA-IX. Data were analysed in conjunction with the clinicopathological characteristics of the patients, KRAS status, response to Bevacizumab and follow up. Results: (1) All the proteins were expressed in the samples, with statistically significant associations between HIF-1α and gender, HIF-2α and left colon, hERG1 and VEGF-A, β1-Integrin and HIF-2α, GLUT-1 and both HIF-1α and HIF-2α, CA-IX and VEGF-A; (2) At the univariate analysis positivity for hERG1, VEGF-A and the active form of HIF-2α (aHIF-2a) , and the G3 histological grade showed a positive impact on Progression Free Survival (PFS); (3) hERG1 and aHIF-2a maintained their positive impact on PFS at the multivariate analysis; (4) hERG1 behaved as a protective factor for PFS independently on KRAS status. Conclusions: hERG1 and aHIF-2a might help to identify patients who would benefit from Bevacizumab treatment.