Abstract
Glutathione peroxidase 8 (GPX8), located in the endoplasmic reticulum, is associated with poor prognosis in several cancers. However, the expression and functions of GPX8 in cancers remain unclear. The purpose of this study was to explore the expression and functions of GPX8 in glioblastoma (GBM). We obtained expression data of GPX8 by accessing the TCGA, CGGA, GEPIA, and TIMER2.0 databases and validated them using western blot and immunohistochemistry. The Kaplan-Meier overall survival curve and Cox regression model were used to evaluate the prognostic value of GPX8 in glioma patients. Gene ontology (GO) and function enrichment analysis were used to investigate the potential function of GPX8 in GBM. Correlation analysis was used to clarify the role of GPX8 in proneural-mesenchymal transition (PMT). We studied the correlation between GPX8 expression and GBM immune infiltration by accessing cBioPortal and TIMER2.0 databases. Here, we demonstrated that GPX8 was significantly upregulated in GBM, and was associated with IDH-wildtype and mesenchymal subtype with poor prognosis. Survival analysis results indicated that GPX8 is an independent prognostic factor for overall survival (OS) in all WHO-grade glioma patients. Through the functional studies, we found that high expression of GPX8 correlated with mesenchymal signature and negatively correlated with proneural signature, indicating that GPX8 might promote PMT in GBM. Finally, based on correlation analysis, we found that the expression of GPX8 was associated with immune infiltration and the IL1/MYD88/IRAK/NF-κB pathway in GBM. Our results show that GPX8 is a key factor affecting the prognosis of GBM patients, and its targeting has the potential to provide a novel therapeutic approach.