Integrative identification of hub genes in development of atrial fibrillation related stroke

BACKGROUND: As the most common arrhythmia, atrial fibrillation (AF) is associated with a significantly increased risk of stroke, which causes high disability and mortality. To date, the underlying mechanism of stroke occurring after AF remains unclear. Herein, we studied hub genes and regulatory pathways involved in AF and secondary stroke and aimed to reveal biomarkers and therapeutic targets of AF-related stroke. METHODS: The GSE79768 and GSE58294 datasets were used to analyze AF- and stroke-related differentially expressed genes (DEGs) to obtain a DEG1 dataset. Weighted correlation network analysis (WGCNA) was used to identify modules associated with AF-related stroke in GSE66724 (DEG2). DEG1 and DEG2 were merged, and hub genes were identified based on protein–protein interaction networks. Gene Ontology terms were used to analyze the enriched pathways. The GSE129409 and GSE70887 were applied to construct a circRNA-miRNA-mRNA network in AF-related stroke. Hub genes were verified in patients using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: We identified 3,132 DEGs in blood samples and 253 DEGs in left atrial specimens. Co-expressed hub genes of EIF4E3, ZNF595, ZNF700, MATR3, ACKR4, ANXA3, SEPSECS-AS1, and RNF166 were significantly associated with AF-related stroke. The hsa_circ_0018657/hsa-miR-198/EIF4E3 pathway was explored as the regulating axis in AF-related stroke. The qRT-PCR results were consistent with the bioinformatic analysis. CONCLUSIONS: Hub genes EIF4E3, ZNF595, ZNF700, MATR3, ACKR4, ANXA3, SEPSECS-AS1, and RNF166 have potential as novel biomarkers and therapeutic targets in AF-related stroke. The hsa_circ_0018657/hsa-miR-198/EIF4E3 axis could play an important role regulating the development of AF-related stroke.