Background: In search of novel biomarkers of response to bevacizumab in metastatic colorectal cancer (mCRC), weanalyzed the expression and prognostic role of several proteins related to angiogenesis. Methods: A retrospective,multicenterstudy on 80 surgical samples from mCRC patients treated in first line with bevacizumab plus chemotherapywas accomplished. The following proteins were analyzed by immunohistochemistry: hERG1 potassium channel, β1-integrin, pAKT, NFkB, HIF-1α, HIF-2α, p53, VEGF-A, GLUT-1, and CA-IX. Data were analyzed in conjunction withthe 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, and CAIXand VEGF-A. (2) At the univariate analysis, positivity for hERG1, VEGF-A, and the active formof HIF-2α (aHIF-2α),and the G3 histological grade showed a positive impact on progression-free survival (PFS). (3) hERG1 and aHIF-2αmaintained their positive impact on PFS at the multivariate analysis. (4) hERG1 behaved as a protective factor forPFS independently on KRAS status. Conclusions: hERG1 and aHIF-2α might help to identify patients who would benefitfrom bevacizumab treatment.
hERG1 and HIF-2α behave as biomarkers of positive response to bevacizumab in metastatic colorectal cancer patients
Perrone G;Caputo D;Coppola R;
2020-01-01
Abstract
Background: In search of novel biomarkers of response to bevacizumab in metastatic colorectal cancer (mCRC), weanalyzed the expression and prognostic role of several proteins related to angiogenesis. Methods: A retrospective,multicenterstudy on 80 surgical samples from mCRC patients treated in first line with bevacizumab plus chemotherapywas accomplished. The following proteins were analyzed by immunohistochemistry: hERG1 potassium channel, β1-integrin, pAKT, NFkB, HIF-1α, HIF-2α, p53, VEGF-A, GLUT-1, and CA-IX. Data were analyzed in conjunction withthe 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, and CAIXand VEGF-A. (2) At the univariate analysis, positivity for hERG1, VEGF-A, and the active formof HIF-2α (aHIF-2α),and the G3 histological grade showed a positive impact on progression-free survival (PFS). (3) hERG1 and aHIF-2αmaintained their positive impact on PFS at the multivariate analysis. (4) hERG1 behaved as a protective factor forPFS independently on KRAS status. Conclusions: hERG1 and aHIF-2α might help to identify patients who would benefitfrom bevacizumab treatment.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
