Investigation of shared genes and regulatory mechanisms associated with coronavirus disease 2019 and ischemic stroke.

Abstract

Clinical associations between coronavirus disease (COVID-19) and ischemic stroke (IS) have been reported. This study aimed to investigate the shared genes between COVID-19 and IS and explore their regulatory mechanisms. Published datasets for COVID-19 and IS were downloaded. Common differentially expressed genes (DEGs) in the two diseases were identified, followed by protein-protein interaction (PPI) network analysis. Moreover, overlapping module genes associated with the two diseases were investigated using weighted correlation network analysis (WGCNA). Through intersection analysis of PPI cluster genes and overlapping module genes, hub-shared genes associated with the two diseases were obtained, followed by functional enrichment analysis and external dataset validation. Moreover, the upstream miRNAs and transcription factors (TFs) of the hub-shared genes were predicted. A total of 91 common DEGs were identified from the clusters of the PPI network, and 129 overlapping module genes were screened using WGCNA. Based on further intersection analysis, four hub-shared genes in IS and COVID-19 were identified, including PDE5A, ITGB3, CEACAM8, and BPI. These hub-shared genes were remarkably enriched in pathways such as ECM-receptor interaction and focal adhesion pathways. Moreover, ITGB3, PDE5A, and CEACAM8 were targeted by 53, 32, and 3 miRNAs, respectively, and these miRNAs were also enriched in the aforementioned pathways. Furthermore, TFs, such as lactoferrin, demonstrated a stronger predicted correlation with the hub-shared genes. The four identified hub-shared genes may participate in crucial mechanisms underlying both COVID-19 and IS and may exhibit the potential to be biomarkers or therapeutic targets for the two diseases.