Comprehensive Bioinformatics Analysis of Gasdermin Family of Glioma.

Abstract

Pyroptosis is a programmed cell death mediated by gasdermins (GSDMs). The prognostic value of pyroptosis-related genes in different tumor types has been gradually demonstrated recently. However, the prognostic impact of GSDMs expression in glioma remains unclear. Here, we present a comprehensive bioinformatic analysis of gasdermin family member gene expression, producing a prognostic model for glioma and creating a competing endogenous RNA (ceRNA) network. The mRNA expression profiles and clinical information of glioma patients were downloaded from TCGA and CGGA. A risk score based on the gasdermin family was constructed in the TCGA cohort and validated in CGGA. The Jurkat cell was used to verify the relationship between pyroptosis and activation-induced cell death (AICD). We identify a significant association between the expression of GSDMD and GSDME and the glioma stage. The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was used to construct a prognostic gene model based on the four prognostic gasdermin family genes (GSDMC, GSDMD, GSDME, and PJVK). This model was able to predict the overall survival of glioma patients with high accuracy. We show that gasdermin family genes are expressed primarily by immune cells, endothelial cells, and neuronal cells in the tumor microenvironment, rather than by malignant tumor cells. T cells were significantly activated in high-risk patients; however, the activation-induced cell death (AICD) pathway was also significantly activated, suggesting widespread expiration of cytotoxic T lymphocytes (CTLs), facilitating tumor progression. We also identify the lncRNA/miR-296-5p/GSDMD regulatory axis as an important player in glioma progression. We have conducted a comprehensive bioinformatic analysis identifying the importance of gasdermin family members in glioma; a prognostic algorithm containing four genes was constructed.