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.

hERG1 and HIF-2α Behave as Biomarkers of Positive Response to Bevacizumab in Metastatic Colorectal Cancer Patients / Iorio, Jessica; Lastraioli, Elena; Tofani, Lorenzo; Petroni, Giulia; Antonuzzo, Lorenzo; Messerini, Luca; Perrone, Giuseppe; Caputo, Damiano; Francesconi, Maria; Amato, Maria Michelina; Cadei, Moris; Arcangeli, Giuseppina; Villanacci, Vincenzo; Boni, Luca; Coppola, Roberto; Di Costanzo, Francesco; Arcangeli, Annarosa. - In: TRANSLATIONAL ONCOLOGY. - ISSN 1936-5233. - ELETTRONICO. - 13:(2020), pp. 1-7. [10.1016/j.tranon.2020.01.001]

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

Iorio, Jessica;Lastraioli, Elena;Tofani, Lorenzo;Petroni, Giulia;Antonuzzo, Lorenzo;Messerini, Luca;Perrone, Giuseppe;Di Costanzo, Francesco;Arcangeli, Annarosa
2020

Abstract

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.
2020
13
1
7
Goal 3: Good health and well-being for people
Iorio, Jessica; Lastraioli, Elena; Tofani, Lorenzo; Petroni, Giulia; Antonuzzo, Lorenzo; Messerini, Luca; Perrone, Giuseppe; Caputo, Damiano; Francesconi, Maria; Amato, Maria Michelina; Cadei, Moris; Arcangeli, Giuseppina; Villanacci, Vincenzo; Boni, Luca; Coppola, Roberto; Di Costanzo, Francesco; Arcangeli, Annarosa
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1184930
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