Unveiling Pyroptosis-Related Hub Genes in Ischemic Stroke Provides Insights for Enhanced Risk Assessment

Background: Stroke is the second-leading global cause of death. The immune storm triggered by ischemia-reperfusion injury after stroke is a crucial damaging factor. This study analyzed the expression of key pyroptosis genes in stroke and their correlation with immune infiltration. Methods: : Middle Cerebral Artery Occlusion datasets were obtained and pyroptosis-related genes were identified. Differential expression and functional analyses of pyroptosis-related genes were performed. Differences in functional enrichment between high-risk and low-risk groups were determined. After selecting pyroptosis-related genes with differential expression, a MCAO diagnostic model was constructed and validated. High and low-risk MCAO groups were constructed for expression and immune cell correlation analysis with pyroptosis-related hub genes. A regulatory network between pyroptosis-related hub genes and miRNA was built, and protein domains were predicted. The expression of key pyroptosis genes was validated in the MCAO rat model. Results: : Twenty-five pyroptosis genes showed differential expression, including four hub genes ( WISP2 , MELK , SDF2L1 , and AURKB ). The high- and low-risk groups showed significant expression differences for WISP2 , MELK and SDF2L1 . In immune infiltration analysis, 12 immune cells exhibited expression differences in MCAO samples. Further analysis demonstrated significant positive correlations between the pyroptosis-related hub gene SDF2L1 and immune cell-activated dendritic cells in the high-risk group and immune cell natural killer cells in the low-risk group. Conclusion: This study identified four pyroptosis-related hub genes, with elevated WISP2 , MELK , and SDF2L1 expression closely associated with the high-risk group. Analysis of inflammatory cell types in immune infiltration provides a theoretical basis for predicting ischemic stroke risk levels and treatment.