Abstract
Despite extensive research on therapeutic targets for glioma, progress has been limited by ineffective treatments. Our aim was to analyze gasdermin (GSDM) family expression, mutations, and clinical relevance in glioma to support clinical decision-making and risk assessment. Glioma specimens were procured from The Cancer Genome Atlas for the purpose of conducting gene expression profile interaction analysis and human protein mapping using various bioinformatics tools, including gene expression profiling interactive analysis, Human Protein Atlas, Kaplan-Meier plotters, cBioPorta, LinkedOmics, database for annotation, visualization and integrated discovery, and R Software. A statistically significant difference was observed with a P < .05. The investigation of mRNA expression levels of GSDM subtypes in 11,079 glioma tissues and 6942 normal brain tissues revealed significant differences, with GSDMA, GSDMD, and GSDME being elevated in glioma compared to normal tissues, while GSDMB showed lower expression. The analysis of mRNA expression levels for GSDM subtypes across 33 tumor and normal tissues showed significant differences in GSDMA, GSDMB, GSDMD, and GSDME. The expression of these genes varied significantly in different glioma subtypes, with higher levels noted in 1p19q non-deletion gliomas and IDH1 wild-type gliomas. Additionally, glioblastoma multiforme displayed increased GSDMA, GSDMD, and GSDME levels compared to other subtypes, with significant associations between gene expression and the clinical World Health Organization stage of gliomas. GSDMB, GSDMC, GSDMD, and GSDME were identified as independent prognostic factors affecting overall survival, with notable differences in recurrence-free survival among different expression groups. Mutation analysis revealed that expansion was the most common mutation in the GSDM family (7% of patients), primarily affecting GSDMD, which had a mutation rate of 5%. Correlation analyses highlighted both positive and negative relationships among GSDM members. Furthermore, enrichment analyses in the database for annotation, visualization and integrated discovery linked 173 associated genes to biological processes like pyroptosis and autophagy, along with involvement in the phagocytic and synaptic vesicle circulation pathways, suggesting that GSDMs may play critical roles in cell death mechanisms and autophagy in glioma, which requires further exploration. Overall, our results suggest a significant involvement of the GSDM group in the pathogenesis of glioma. GSDMB, GSDMC, GSDMD, and GSDME have been identified as potential prognostic and predictive markers for glioma, while GSDMs show promise as therapeutic targets for this type of brain tumor.