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

Abstract

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.