Integrated analysis identifies the IL6/JAK/STAT signaling pathway and the estrogen response pathway associated with the pathogenesis of intracranial aneurysms.

Objective: We intended to identify the potential key biomarker and pathways that correlated with infiltrating immune cells during the pathogenesis of intracranial aneurysms (IA), to develop a diagnostic model, and to predict therapeutic drugs. Methods: Three datasets containing intracranial aneurysm tissue samples and normal artery control samples from Gene Expression Omnibus (GEO) were included. Gene-set variation analysis(GSVA) and gene set enrichment analysis (GSEA) were conducted to find the significant differentially expressed pathways in IA formation. The least absolute shrinkage and selection operator (LASSO) regression and the multivariate logistic regression analysis were performed to identify the characteristic genes in the IL6/JAK/STAT signaling pathway (ISP) and the estrogen response pathway (ERP). A diagnostic model was constructed. xCell was used to identify immune cell types in IA pathogenesis. We used the weighted gene co-expression network analysis (WGCNA) algorithm to explore the correlations between the key modules and the four traits. Potential therapeutic drugs were investigated in Enrichr and Drugbank database. Results: The ISP is significant positively correlated with IA onset. The biological function of the ISP is positively correlated with that of the ERP, and is significantly associated with immune cells activities. Conclusions: We identified that the ISP was one of the most significant positively correlated pathways in IA onset, and it was activated in this process concordant with the ERP and immune responses. Except for beneficial effects, complex and multiple roles of estrogen may be involved in IA formation. STAT2 could be a potential biomarker and a promising therapeutic target of IA pathogenesis.