Expression Analysis of α5 Integrin Subunit Reveals Its Upregulation as a Negative Prognostic Biomarker for Glioblastoma
| Autor: | Pascal Caillet, Nelly Etienne-Selloum, Jean-Marc Constans, Monique Dontenwill, Mathieu Boone, Henri Sevestre, Bruno Chauffert, Diana Bello-Roufai, Alexandre Coutte, Sophie Martin, Julien Prades, Stéphanie Trudel, Laurence Choulier, Christine Desenclos |
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| Přispěvatelé: | Laboratoire de Bioimagerie et Pathologies (LBP), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), CHU Amiens-Picardie, Unité de génétique médicale et oncogénétique [CHU Amiens Picardie] |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Oncology
medicine.medical_specialty Methyltransferase Protein subunit Integrin Stupp protocol resistance Pharmaceutical Science Recursive partitioning [SDV.CAN]Life Sciences [q-bio]/Cancer Immunofluorescence Article 03 medical and health sciences 0302 clinical medicine Pharmacy and materia medica Downregulation and upregulation Internal medicine Drug Discovery medicine 030304 developmental biology 0303 health sciences Temozolomide medicine.diagnostic_test biology business.industry integrin α5 glioblastoma 3. Good health RS1-441 030220 oncology & carcinogenesis biology.protein Molecular Medicine Biomarker (medicine) biomarker Medicine business medicine.drug |
| Zdroj: | Pharmaceuticals Pharmaceuticals, MDPI, 2021, 14 (9), pp.882. ⟨10.3390/ph14090882⟩ Pharmaceuticals, Vol 14, Iss 882, p 882 (2021) Volume 14 Issue 9 |
| ISSN: | 1424-8247 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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