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

Abstract 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.