Bioinformatics-based analysis of the mechanism of tirofiban-mediated immune response in the treatment of ischemic stroke

Objective: Ischemic stroke is a common cerebrovascular disease that poses a serious threat to human health. However, its immune regulatory mechanism still needs to be elucidated, and patients have different responses to immunotherapy drugs. Therefore, it is urgent to elucidate the immune regulatory mechanism of ischemic stroke and search for biomarkers that have a positive response to immunotherapy for ischemic stroke. Methods: From GEO database ( https://www.ncbi.nlm.nih.gov/geo/ ) Obtain the expression profile information of GSE16561 and GSE37587, perform batch processing on the merged two datasets, and use limma packages to identify differentially expressed genes to determine the differences between the normal group and the ischemic stroke group. Subsequently, GO/KEGG enrichment analysis was performed. Then, through weighted co expression network analysis, feature module genes closely related to immune infiltration in ischemic stroke were screened. The intersection of characteristic module genes and differentially expressed genes was used to construct PPI networks. Subsequently, the retained genes will be screened for potential core genes through three types of machine learning: random forest, xgboost, and lasso. By using consistency clustering, ischemic stroke patients are classified and potential typing genes associated with immune cell infiltration are identified. Finally, by constructing ROC curves and nomogram models, the diagnostic performance of genotyping genes is evaluated, and the target genes obtained are molecular docked with tirofiban. Results: A total of 673 genes were detected to have differences in expression, including 161 downregulated genes and 512 upregulated genes. These genes are mainly involved in biological processes such as neutrophil granulosa shedding and cell membrane, and are related to signaling pathways such as leishmaniasis and hematopoietic cell development. WGCNA analysis identified 225 genes related to immune infiltration in ischemic stroke, and by constructing a PPI network, 156 genes were found to have good interactions. Subsequently, 16 genes were screened through machine learning, namely ANTXR2; BAZ1A; CLEC4D; IL18RAP; MMP9; NOTCH2; PAK2; SLC2A3; TAOK1; TLR2; DHRS9; GYG1; HMFN0839; MOSC1; OLFM4; TCN1. These genes exhibit good diagnostic performance and TLR2 has been found to be a potential target of tirofiban. Conclusion: Tirofiban may mediate an immune response through the TLR2-related pathway for the treatment of ischemic stroke. Four “Batches” Innovation Project of Invigorating Medical through Science and Technology of Shanxi Province, Innovative Teaching Reform Project of Shanxi Universities This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.