Investigation of shared molecular mechanisms underlying sepsis and heart failure via integrated analysis of multiple microarray data

Abstract

Abstract Objective: This study aimed to mine shared genes and related molecular mechanisms of sepsis and heart failure (HF). Methods: Differentially expressed genes (DEGs) in sepsis and HF samples were identified using discovery datasets (GSE28750 and GSE57345). Weighted gene coexpression network analysis (WGCNA) of the DEGs was performed to identify sepsis- and HF-related gene coexpression modules. Shared genes of the two diseases were identified, followed by functional enrichment analysis, protein‒protein interaction (PPI) analysis, and expression validation using validation datasets (GSE65682 and GSE84796). Moreover, diagnostic performance, immune cell infiltration, and gene set enrichment analyses for hub-shared genes were conducted. Results: In total, 5407 and 2042 DEGs in sepsis and HF samples, respectively, were identified based on GSE28750 and GSE57345. WGCNA revealed five sepsis-related modules containing 2972 genes and three HF-related modules containing 982 genes; 170 shared genes of the two diseases were obtained. Four hub-shared genes of the two diseases were identified, including RRS1, IMP4, RPLP0, and NOP16, by PPI analysis and expression validation with external datasets. The four hub-shared genes had high diagnostic performance, with AUC [Editor1] values higher than 0.7 in the four datasets. Moreover, there was a significantly negative correlation between RRS1 and M0 macrophages and between IMP4 macrophages and plasma cells in the two diseases; these genes were significantly enriched in ribosome assembly and biogenesis processes. Conclusion: Four genes, RRS1, IMP4, RPLP0, and NOP16, may be key common regulators in sepsis and HF and serve as diagnostic biomarkers and therapeutic targets for these two diseases. Abbreviations are typically defined the first time the term is used within the abstract and again in the main text and then used exclusively throughout the remainder of the document. Please consider adhering to this convention. The target journal may have a list of abbreviations that are considered common enough that they do not need to be defined.