hERG1 and HIF-2α Behave as Biomarkers of Positive Response to Bevacizumab in Metastatic Colorectal Cancer Patients.
Journal
Translational oncology
ISSN: 1936-5233
Titre abrégé: Transl Oncol
Pays: United States
ID NLM: 101472619
Informations de publication
Date de publication:
Mar 2020
Mar 2020
Historique:
received:
19
07
2019
accepted:
09
01
2020
pubmed:
28
2
2020
medline:
28
2
2020
entrez:
28
2
2020
Statut:
ppublish
Résumé
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. 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. (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. hERG1 and aHIF-2α might help to identify patients who would benefit from bevacizumab treatment.
Sections du résumé
BACKGROUND
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
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
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
CONCLUSIONS
hERG1 and aHIF-2α might help to identify patients who would benefit from bevacizumab treatment.
Identifiants
pubmed: 32105990
pii: S1936-5233(19)30376-6
doi: 10.1016/j.tranon.2020.01.001
pmc: PMC7044526
pii:
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100740Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
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