Bioinformatics analysis reveals major hub genes involved with extracellular matrix and inflammatory and endocrine pathways associated with intracranial aneurysm tissue

BackgroundIntracranial aneurysm (IA) pathogenesis involves complex interplay between genetic predisposition and focal extracellular matrix (ECM) membrane degradation and inflammatory processes. We aimed to identify key differentially expressed genes (DEGs) that serve as hub genes (major genes with large networks) associated with IAs.MethodsWe conducted a comprehensive search of available Gene Expression Omnibus (GEO) databases for IA tissue from database inception to January 2024. This resulted in five GEO datasets, of which four were included as the discovery set, consisting of tissue from 28 IAs and 34 controls. DEGs were identified and used for enrichment analysis in evaluating Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes database pathways. A protein-protein interaction (PPI) DEG network was constructed to pinpoint interactions with other DEGs. The fifth GEO dataset was used to validate hub gene expressions.ResultsWe identified 1864 DEGs: 963 downregulated, 901 upregulated. Three gene clusters were linked to critical biological processes; notably, inflammatory response (GO:006954, false discovery rate [FDR] = 7.12 × 10^-25), muscle contraction (GO:0006936, FDR = 1.1 × 10^-3), and endocrine-related phosphatidylcholine sterol O-acyltransferase activator activity (GO:0060228, <i>p</i>_adj = 3.2 × 10^-2) pathways. Eleven hub genes were identified, of which eight (COL1A, CXCR4, IL10, CXCL8, ESR1, APOE, RN1, and IGF1) were validated.ConclusionsTo our knowledge, this study represents the largest bioinformatics analysis to date on IAs, resulting in identification of 11 hub genes involved in ECM and immunologic pathways. These findings are consistent with existing literature; however, the potential involvement of endocrine-related processes, such as estrogen receptor signaling and cholesterol metabolism, is particularly intriguing and has not been previously well studied in this context.