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

Translational Oncology. 2020;13(3)

 

Journal Homepage

Journal Title: Translational Oncology

ISSN: 1944-7124 (Print); 1936-5233 (Online)

Publisher: Elsevier

LCC Subject Category: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens

Country of publisher: Netherlands

Language of fulltext: English

Full-text formats available: PDF, HTML

 

AUTHORS


Jessica Iorio (Department of Experimental and Clinical Medicine, University of Florence, Italy; Department of Medical Biotechnologies, University of Siena, Italy)

Elena Lastraioli (Department of Experimental and Clinical Medicine, University of Florence, Italy)

Lorenzo Tofani (Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy)

Giulia Petroni (Department of Experimental and Clinical Medicine, University of Florence, Italy)

Lorenzo Antonuzzo (Department of Medical Biotechnologies, University of Siena, Italy; Medical Oncology, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy)

Luca Messerini (Department of Experimental and Clinical Medicine, University of Florence, Italy)

Giuseppe Perrone (Department of Pathology, Campus Bio-Medico University of Rome, Italy)

Damiano Caputo (Department of General Surgery, Campus Bio-Medico University of Rome, Italy)

Maria Francesconi (Department of Pathology, Campus Bio-Medico University of Rome, Italy)

Maria Michelina Amato (Department of Pathology, Campus Bio-Medico University of Rome, Italy)

Moris Cadei (Institute of Pathology, ASST Spedali Civili di Brescia, Brescia, Italy)

Giuseppina Arcangeli (Department of Medical Oncology, ASST Spedali Civili di Brescia, Brescia, Italy)

Vincenzo Villanacci (Institute of Pathology, ASST Spedali Civili di Brescia, Brescia, Italy)

Luca Boni (Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy)

Roberto Coppola (Department of General Surgery, Campus Bio-Medico University of Rome, Italy)

Francesco Di Costanzo (Medical Oncology, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy)

Annarosa Arcangeli (Department of Experimental and Clinical Medicine, University of Florence, Italy; Address all correspondence to: Annarosa Arcangeli, M.D., Ph.D. Department of Clinical and Experimental Medicine, Internal Medicine Section, Viale GB Morgagni, 50, 50134 Florence, Italy.)

EDITORIAL INFORMATION

Peer review

Editorial Board

Instructions for authors

Time From Submission to Publication: 18 weeks

 

Abstract | Full Text

Background: In search of novel biomarkers of response to bevacizumab in metastatic colorectal cancer (mCRC), we analyzed 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 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 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, and CA-IX and VEGF-A. (2) At the univariate analysis, positivity for hERG1, VEGF-A, and the active form of HIF-2α (aHIF-2α), and the G3 histological grade showed a positive impact on progression-free survival (PFS). (3) hERG1 and aHIF-2α 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-2α might help to identify patients who would benefit from bevacizumab treatment.