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Expression Analysis of α5 Integrin Subunit Reveals Its Upregulation as a Negative Prognostic Biomarker for Glioblastoma

Integrin α5β1 was suggested to be involved in glioblastoma (GBM) aggressiveness and treatment resistance through preclinical studies and genomic analysis in patients. However, further protein expression data are still required to confirm this hypothesis. In the present study, we investigated by immu...

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Autores principales: Etienne-Selloum, Nelly, Prades, Julien, Bello-Roufai, Diana, Boone, Mathieu, Sevestre, Henri, Trudel, Stéphanie, Caillet, Pascal, Coutte, Alexandre, Desenclos, Christine, Constans, Jean-Marc, Martin, Sophie, Choulier, Laurence, Chauffert, Bruno, Dontenwill, Monique
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465081/
https://www.ncbi.nlm.nih.gov/pubmed/34577582
http://dx.doi.org/10.3390/ph14090882
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author Etienne-Selloum, Nelly
Prades, Julien
Bello-Roufai, Diana
Boone, Mathieu
Sevestre, Henri
Trudel, Stéphanie
Caillet, Pascal
Coutte, Alexandre
Desenclos, Christine
Constans, Jean-Marc
Martin, Sophie
Choulier, Laurence
Chauffert, Bruno
Dontenwill, Monique
author_facet Etienne-Selloum, Nelly
Prades, Julien
Bello-Roufai, Diana
Boone, Mathieu
Sevestre, Henri
Trudel, Stéphanie
Caillet, Pascal
Coutte, Alexandre
Desenclos, Christine
Constans, Jean-Marc
Martin, Sophie
Choulier, Laurence
Chauffert, Bruno
Dontenwill, Monique
author_sort Etienne-Selloum, Nelly
collection PubMed
description Integrin α5β1 was suggested to be involved in glioblastoma (GBM) aggressiveness and treatment resistance through preclinical studies and genomic analysis in patients. However, further protein expression data are still required to confirm this hypothesis. In the present study, we investigated by immunofluorescence the expression of integrin α5 and its prognostic impact in a glioblastoma series of patients scheduled to undergo the Stupp protocol as first-line treatment for GBM. The integrin α5 protein expression level was estimated in each tumor by the mean fluorescence intensity (MFI) and allowed us to identify two subpopulations showing either a high or low expression level. The distribution of patients in both subpopulations was not significantly different according to age, gender, recursive partitioning analysis (RPA) prognostic score, molecular markers or surgical and medical treatment. A high integrin α5 protein expression level was associated with a high risk of recurrence (HR = 1.696, 95% CI 1.031–2.792, p = 0.0377) and reduced overall survival (OS), even more significant in patients who completed the Stupp protocol (median OS: 15.6 vs. 22.8 months; HR = 2.324; 95% CI 1.168–4.621, p = 0.0162). In multivariate analysis, a high integrin α5 protein expression level was confirmed as an independent prognostic factor in the subpopulation of patients who completed the temozolomide-based first-line treatment for predicting OS over age, extent of surgery, RPA score and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation (p = 0.029). In summary, for the first time, our study validates that a high integrin α5 protein expression level is associated with poor prognosis in GBM and confirms its potential as a therapeutic target implicated in the Stupp protocol resistance.
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spelling pubmed-84650812021-09-27 Expression Analysis of α5 Integrin Subunit Reveals Its Upregulation as a Negative Prognostic Biomarker for Glioblastoma Etienne-Selloum, Nelly Prades, Julien Bello-Roufai, Diana Boone, Mathieu Sevestre, Henri Trudel, Stéphanie Caillet, Pascal Coutte, Alexandre Desenclos, Christine Constans, Jean-Marc Martin, Sophie Choulier, Laurence Chauffert, Bruno Dontenwill, Monique Pharmaceuticals (Basel) Article Integrin α5β1 was suggested to be involved in glioblastoma (GBM) aggressiveness and treatment resistance through preclinical studies and genomic analysis in patients. However, further protein expression data are still required to confirm this hypothesis. In the present study, we investigated by immunofluorescence the expression of integrin α5 and its prognostic impact in a glioblastoma series of patients scheduled to undergo the Stupp protocol as first-line treatment for GBM. The integrin α5 protein expression level was estimated in each tumor by the mean fluorescence intensity (MFI) and allowed us to identify two subpopulations showing either a high or low expression level. The distribution of patients in both subpopulations was not significantly different according to age, gender, recursive partitioning analysis (RPA) prognostic score, molecular markers or surgical and medical treatment. A high integrin α5 protein expression level was associated with a high risk of recurrence (HR = 1.696, 95% CI 1.031–2.792, p = 0.0377) and reduced overall survival (OS), even more significant in patients who completed the Stupp protocol (median OS: 15.6 vs. 22.8 months; HR = 2.324; 95% CI 1.168–4.621, p = 0.0162). In multivariate analysis, a high integrin α5 protein expression level was confirmed as an independent prognostic factor in the subpopulation of patients who completed the temozolomide-based first-line treatment for predicting OS over age, extent of surgery, RPA score and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation (p = 0.029). In summary, for the first time, our study validates that a high integrin α5 protein expression level is associated with poor prognosis in GBM and confirms its potential as a therapeutic target implicated in the Stupp protocol resistance. MDPI 2021-08-30 /pmc/articles/PMC8465081/ /pubmed/34577582 http://dx.doi.org/10.3390/ph14090882 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Etienne-Selloum, Nelly
Prades, Julien
Bello-Roufai, Diana
Boone, Mathieu
Sevestre, Henri
Trudel, Stéphanie
Caillet, Pascal
Coutte, Alexandre
Desenclos, Christine
Constans, Jean-Marc
Martin, Sophie
Choulier, Laurence
Chauffert, Bruno
Dontenwill, Monique
Expression Analysis of α5 Integrin Subunit Reveals Its Upregulation as a Negative Prognostic Biomarker for Glioblastoma
title Expression Analysis of α5 Integrin Subunit Reveals Its Upregulation as a Negative Prognostic Biomarker for Glioblastoma
title_full Expression Analysis of α5 Integrin Subunit Reveals Its Upregulation as a Negative Prognostic Biomarker for Glioblastoma
title_fullStr Expression Analysis of α5 Integrin Subunit Reveals Its Upregulation as a Negative Prognostic Biomarker for Glioblastoma
title_full_unstemmed Expression Analysis of α5 Integrin Subunit Reveals Its Upregulation as a Negative Prognostic Biomarker for Glioblastoma
title_short Expression Analysis of α5 Integrin Subunit Reveals Its Upregulation as a Negative Prognostic Biomarker for Glioblastoma
title_sort expression analysis of α5 integrin subunit reveals its upregulation as a negative prognostic biomarker for glioblastoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465081/
https://www.ncbi.nlm.nih.gov/pubmed/34577582
http://dx.doi.org/10.3390/ph14090882
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