Expression Analysis of α5 Integrin Subunit Reveals Its Upregulation as a Negative Prognostic Biomarker for Glioblastoma - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Pharmaceuticals Année : 2021

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

Mathieu Boone
  • Fonction : Auteur
  • PersonId : 1149851
  • IdRef : 157767957
Henri Sevestre
Pascal Caillet
Alexandre Coutte
  • Fonction : Auteur
  • PersonId : 1100561
  • IdRef : 137587589
Christine Desenclos
  • Fonction : Auteur
  • PersonId : 1149981
  • IdRef : 148178790
Jean-Marc Constans
Bruno Chauffert

Résumé

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.

Domaines

Cancer
Fichier principal
Vignette du fichier
ETIENNE et al. PHARMACEUTICALS 2021.pdf (2.24 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-03436842 , version 1 (25-11-2021)

Identifiants

Citer

Nelly Etienne-Selloum, Julien Prades, Diana Bello-Roufai, Mathieu Boone, Henri Sevestre, et al.. Expression Analysis of α5 Integrin Subunit Reveals Its Upregulation as a Negative Prognostic Biomarker for Glioblastoma. Pharmaceuticals, 2021, 14 (9), pp.882. ⟨10.3390/ph14090882⟩. ⟨hal-03436842⟩
14 Consultations
23 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More