Abstract
Background: The prognosis of Glioblastoma (GBM) remains poor. Low-grade gliomas (LGG) are known to progress to GBM whilst the chance of survival decreases. The TNF-Receptor CD40 and the ligand CD40L have shown first value as biomarker regarding the prognosis of GBM. The present study evaluates the role of CD40/CD40L in LGG and GBM differentiating IDH-wild-type and IDH-mutant GBM. All data are based on patient-derived samples and expression was measured by real-time PCR.
Methods
Samples of 75 grade II gliomas and 40 GBM were included in the study. RT-PCR was performed to measure CD40/CD40L expression, using SDHA as housekeeper. The TCGA-Data was used to run analysis on mRNA-expression.
Results
We could show, that patients with LGG and CD40 overexpression present shorter progression-free (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 gliomas show higher CD40 expression compared to primary grade II gliomas (p=0.0028). As in LGG, CD40 was a negative marker for overall survival (12 vs. 10 months, Hazard Ratio 0.5178, p=0.0491) in GBM. In this context, we could show a higher CD40 expression in IDH-wild-type GBM compared to IDH-mutant GBM. The strong cohorts of the TCGA datasets “Brain Lower Grade Glioma” and “Glioblastoma” enforced our findings with similar results for PFS and OS in LGG and GBM. CD40L showed no correlation with survival data.
Conclusion
Summarizing, high expression of CD40 shows significant association with poor outcome in LGG and GBM; and is overexpressed in IDH-wild-type GBM.