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

Kai Huang1, Xi Fan1, Yuwen Jiang1

  • 1Department of Cardiothoracic Surgery, Huashan Hospital of Fudan University, Shanghai, China.

Plos One
|March 23, 2023
PubMed

Insights

Atrial fibrillation (AF) stroke mechanisms were investigated using bioinformatics. Key genes like EIF4E3 and pathways were identified as potential biomarkers and therapeutic targets for AF-related stroke.

Area of Science:

  • Genomics and Bioinformatics
  • Cardiovascular Research
  • Molecular Biology

Background:

  • Atrial fibrillation (AF) is the most common arrhythmia, significantly increasing stroke risk, mortality, and disability.
  • The precise mechanisms linking AF to secondary stroke remain incompletely understood.
  • Identifying biomarkers and therapeutic targets for AF-related stroke is crucial.

Purpose of the Study:

  • To investigate the underlying molecular mechanisms of stroke in patients with atrial fibrillation.
  • To identify key genes and regulatory pathways involved in AF-related stroke.
  • To discover potential biomarkers and therapeutic targets for AF-related stroke.

Main Methods:

  • Differential gene expression analysis of AF and stroke datasets (GSE79768, GSE58294, GSE66724).
  • Weighted gene co-expression network analysis (WGCNA) to identify AF-stroke associated modules.
  • Protein-protein interaction network analysis to identify hub genes.
  • Gene Ontology (GO) enrichment analysis for pathway identification.
  • Construction of a circRNA-miRNA-mRNA network (GSE129409, GSE70887).
  • Validation of hub genes using quantitative real-time polymerase chain reaction (qRT-PCR).

Main Results:

  • Identified 3,132 differentially expressed genes (DEGs) in blood and 253 DEGs in left atrial specimens.
  • Eight co-expressed hub genes (EIF4E3, ZNF595, ZNF700, MATR3, ACKR4, ANXA3, SEPSECS-AS1, RNF166) were significantly associated with AF-related stroke.
  • The hsa_circ_0018657/hsa-miR-198/EIF4E3 pathway was identified as a key regulatory axis.
  • Bioinformatic findings were validated by qRT-PCR in patient samples.

Conclusions:

  • The identified hub genes (EIF4E3, ZNF595, ZNF700, MATR3, ACKR4, ANXA3, SEPSECS-AS1, RNF166) show potential as novel biomarkers and therapeutic targets for AF-related stroke.
  • The hsa_circ_0018657/hsa-miR-198/EIF4E3 axis may play a critical role in the pathogenesis of AF-related stroke.
  • Further research into these molecular targets could lead to improved clinical management of AF-related stroke.
Abstract

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