Integrated bioinformatics analysis identifies RPS27A and PPP2R1A as shared hub genes in heart failure and COVID-19

Heart failure (HF) and COVID-19 are distinct but serious conditions with overlapping features such as systemic inflammation and multiorgan involvement. Both may share underlying molecular mechanisms, but the common genetic contributors remain poorly understood. This study aimed to identify shared key genes involved in HF and COVID-19 using integrative bioinformatics analysis.

Two transcriptomic datasets GSE76701 (HF myocardial tissue) and GSE190496 (COVID-19 lung tissue)-were retrieved from the GEO database. Differentially expressed genes (DEGs) were identified using the limma package. Weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) network analysis were used to identify hub genes. Functional enrichment (GO, KEGG, GSEA), immune infiltration (CIBERSORT), disease association (CTD), and miRNA prediction (TargetScan) analyses were also performed.

A total of 511 overlapping DEGs were identified. Enrichment analyses revealed involvement of pathways such as mTOR, insulin, and thyroid hormone signaling. WGCNA and PPI network analysis identified five core genes, including RPS27A and PPP2R1A, both of which were significantly upregulated in HF and COVID-19 samples. Immune infiltration analysis revealed increased macrophage fractions. miRNA predictions suggested PPP2R1A is potentially regulated by miR-497-5p, miR-15b-5p, and miR-15a-5p.

RPS27A and PPP2R1A may serve as common molecular regulators in HF and COVID-19. These findings offer potential cross-disease biomarkers and therapeutic targets for conditions driven by inflammation and immune dysregulation.