AUTHOR=Wang Xuan , Liu Xueyuan 

TITLE=Exploration of the shared gene signatures and molecular mechanisms between cardioembolic stroke and ischemic stroke

JOURNAL=Frontiers in Neurology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1567902

DOI=10.3389/fneur.2025.1567902

ISSN=1664-2295

ABSTRACT=IntroductionThis study aimed to investigate the shared molecular mechanisms underlying cardioembolic stroke (CS) and ischemic stroke (IS) using integrated bioinformatics analysis.MethodsMicroarray datasets for the CS (GSE58294, blood samples from CS and controls) and IS (GSE16561, blood from IS and controls; GSE22255, peripheral blood mononuclear cells from IS and matched controls) were acquired from the Gene Expression Omnibus database. Differential expression analysis and weighted gene co-expression network analysis were utilized to identify shared genes between the two diseases. Protein-protein interaction (PPI) network and topology analyses were conducted to identify the core shared genes. Three machine learning algorithms were employed to detect biomarkers from the core shared genes, and the diagnostic value of the hub genes was evaluated by establishing a predictive nomogram. Immune infiltration was evaluated using single-sample gene set enrichment analysis (ssGSEA), and pathways were analyzed with gene set enrichment analysis.ResultsThere were 125 shared up-regulated genes and 2 shared down-regulated between CS and IS, which were mainly involved in immune inflammatory response-related biological functions. The Maximum Clique Centrality algorithm identified 25 core shared genes in the PPI network constructed using the shared genes. ABCA1, CLEC4E, and IRS2 were identified as biomarkers for both CS and IS and performed well in predicting the onset risk of CS and IS. All three biomarkers were highly expressed in both CS and IS compared to their corresponding controls. These biomarkers significantly correlated with neutrophil infiltration and autophagy activation in both CS and IS. Particularly, all three biomarkers were associated with the activation of neutrophil extracellular trap formation, but only in the IS.ConclusionABCA1, CLEC4E, and IRS2 were identified as potential key biomarkers and therapeutic targets for CS and IS. Autophagy and neutrophil infiltration may represent the common mechanisms linking these two diseases.