Expression of CD40 Correlates Negatively with Overall and Progression-Free Survival of Low- and High-Grade Gliomas.


Journal

World neurosurgery
ISSN: 1878-8769
Titre abrégé: World Neurosurg
Pays: United States
ID NLM: 101528275

Informations de publication

Date de publication:
Oct 2019
Historique:
received: 13 03 2019
revised: 12 05 2019
accepted: 13 05 2019
pubmed: 28 5 2019
medline: 21 1 2020
entrez: 25 5 2019
Statut: ppublish

Résumé

Low-grade gliomas (LGGs) are known to progress to glioblastoma (GBM), decreasing the chances of survival. The tumor necrosis factor receptor CD40 and its ligand CD40L have shown value as biomarkers for GBM. The present study evaluated the role of CD40/CD40L in LGG and GBM in differentiating isocitrate dehydrogenase (IDH) wild-type and IDH-mutant GBM. The present study was based on patient-derived samples (74 grade II gliomas, 36 grade III gliomas, and 40 cases of GBM) and expression analysis using real-time polymerase chain reaction. Open-access data from The Cancer Genome Atlas (TCGA) and the strong cohorts of TCGA data sets "brain lower grade glioma" and "glioblastoma" were used to run the analysis on mRNA expression as a validation data set. We found that patients with LGG and CD40 overexpression experienced shorter progression-free survival (43 vs. 29 months; hazard ratio, 0.5715; P = 0.0262) and overall survival (116 vs. 54 months; hazard ratio, 0.3431; P < 0.0001). Consistently, relapsed grade II glioma showed greater CD40 expression compared with primary grade II glioma (P = 0.0028). Just as with LGG, CD40 was a negative marker for overall survival in GBM (12 vs. 10 months; hazard ratio, 0.5178; P = 0.0491). In this context, we found greater CD40 expression in IDH wild-type GBM than in IDH-mutant GBM. The data obtained from TCGA supported our findings, with similar results for PFS and OS in LGG and GBM. CD40L expression showed no correlation with the survival data. High CD40 expression showed a significant correlation with poor outcomes for both LGG and GBM and was overexpressed in IDH wild-type GBM.

Sections du résumé

BACKGROUND BACKGROUND
Low-grade gliomas (LGGs) are known to progress to glioblastoma (GBM), decreasing the chances of survival. The tumor necrosis factor receptor CD40 and its ligand CD40L have shown value as biomarkers for GBM. The present study evaluated the role of CD40/CD40L in LGG and GBM in differentiating isocitrate dehydrogenase (IDH) wild-type and IDH-mutant GBM.
METHODS METHODS
The present study was based on patient-derived samples (74 grade II gliomas, 36 grade III gliomas, and 40 cases of GBM) and expression analysis using real-time polymerase chain reaction. Open-access data from The Cancer Genome Atlas (TCGA) and the strong cohorts of TCGA data sets "brain lower grade glioma" and "glioblastoma" were used to run the analysis on mRNA expression as a validation data set.
RESULTS RESULTS
We found that patients with LGG and CD40 overexpression experienced shorter progression-free survival (43 vs. 29 months; hazard ratio, 0.5715; P = 0.0262) and overall survival (116 vs. 54 months; hazard ratio, 0.3431; P < 0.0001). Consistently, relapsed grade II glioma showed greater CD40 expression compared with primary grade II glioma (P = 0.0028). Just as with LGG, CD40 was a negative marker for overall survival in GBM (12 vs. 10 months; hazard ratio, 0.5178; P = 0.0491). In this context, we found greater CD40 expression in IDH wild-type GBM than in IDH-mutant GBM. The data obtained from TCGA supported our findings, with similar results for PFS and OS in LGG and GBM. CD40L expression showed no correlation with the survival data.
CONCLUSION CONCLUSIONS
High CD40 expression showed a significant correlation with poor outcomes for both LGG and GBM and was overexpressed in IDH wild-type GBM.

Identifiants

pubmed: 31125770
pii: S1878-8750(19)31386-5
doi: 10.1016/j.wneu.2019.05.112
pii:
doi:

Substances chimiques

Biomarkers, Tumor 0
CD40 Antigens 0
Isocitrate Dehydrogenase EC 1.1.1.41

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e17-e25

Informations de copyright

Copyright © 2019 Elsevier Inc. All rights reserved.

Auteurs

Jan-Michael Werner (JM)

Laboratory for Neurooncology and Experimental Neurosurgery, Department of General Neurosurgery, Center for Neurosurgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.

Saskia Kuhl (S)

Laboratory for Neurooncology and Experimental Neurosurgery, Department of General Neurosurgery, Center for Neurosurgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.

Katharina Ulrich (K)

German Center for Neurodegenerative Diseases, Bonn, Germany.

Boris Krischek (B)

Laboratory for Neurooncology and Experimental Neurosurgery, Department of General Neurosurgery, Center for Neurosurgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.

Pantelis Stavrinou (P)

Laboratory for Neurooncology and Experimental Neurosurgery, Department of General Neurosurgery, Center for Neurosurgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.

Roland Goldbrunner (R)

Laboratory for Neurooncology and Experimental Neurosurgery, Department of General Neurosurgery, Center for Neurosurgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.

Marco Timmer (M)

Laboratory for Neurooncology and Experimental Neurosurgery, Department of General Neurosurgery, Center for Neurosurgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; Max Planck Institute for Metabolism Research, Cologne, Germany. Electronic address: marco.timmer@uk-koeln.de.

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Classifications MeSH