Gasdermin Family as an Underlying Key Factor in Glioma

Abstract Pyroptosis is a programmed cell death process 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. We identify a significant association between expression of GSDMD and GSDME and glioma stage, and demonstrate that high expression of both GSDMD and GSDME is associated with shorter survival. Conversely, low expression of GSDMC was associated with shorter survival. 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 overall survival of glioma patients with high accuracy. We show that gasdermin family genes are expressed primary 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. In conclusion, we have conducted a comprehensive bioinformatic analysis identifying the importance of gasdermin family members in glioma; a prognostic algorithm containing 4 genes (GSDMC, GSDMD, GSDME, and PJVK) was constructed.