Identifying Pyroptosis-Hub Genes and Inflammation Cell Type-Related Genes in Ischemic Stroke

Stroke is the second-leading global cause of death. The damage attributed to the immune storm triggered by ischemia–reperfusion injury (IRI) post-stroke is substantial. However, data on the transcriptomic dynamics of pyroptosis in IRI are limited. This study aimed to analyze the expression of key pyroptosis genes in stroke and their correlation with immune infiltration. Pyroptosis-related genes were identified from the obtained middle cerebral artery occlusion (MCAO) datasets. Differential expression and functional analyses of pyroptosis-related genes were performed, and differences in functional enrichment between high-risk and low-risk groups were determined. An MCAO diagnostic model was constructed and validated using selected pyroptosis-related genes with differential expression. 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 also constructed, and protein domains were predicted. The expression of key pyroptosis genes was validated using an MCAO rat model. Twenty-five pyroptosis genes showed differential expression, including four hub genes, namely WISP2, MELK, SDF2L1, and AURKB. Characteristic genes were verified using real-time quantitative PCR analyses. The high- and low-risk groups showed significant expression differences for WISP2, MELK, and SDF2L1. In immune infiltration analysis, 12 immune cells showed differences in expression 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. This study identified four pyroptosis-related hub genes, with elevated WISP2, MELK, and SDF2L1 expression closely associated with the high-risk group. The analysis of inflammatory cell types in immune infiltration can predict ischemic stroke risk levels and help to facilitate treatment.