Identification of the pivotal differentially expressed genes and pathways involved in Staphylococcus aureus-induced infective endocarditis by using bioinformatics analysis.

ABSTRACT

OBJECTIVE: Infective endocarditis (IE), particularly by Staphylococcus aureus, is an uncommon bacteremia-associated infection of the endocardium and cardiac valves. Herein, we evaluated predictive noninvasive biomarkers for IE caused by S. aureus through bioinformatics analysis. MATERIALS AND METHODS: Staphylococcus aureus-associated and IE-associated differentially expressed genes (DEGs) were identified by bioinformatics analysis of the GSE6269 and GSE29161 Gene Expression Omnibus (GEO) datasets. The DEGs were analyzed with the LIMMA package, and the coregulated genes were chosen as the intersection of DEGs between the two datasets, called common differentially expressed genes (CDEGs). The enrichment study of CDEGs was subsequently performed with the DAVID and KOBAS web resources. Finally, protein-protein interaction (PPI) network, microRNA (miRNA)-transcription factor (TF)-mRNA (messenger RNA) regulatory network, and the network of drug-genes were identified. RESULTS: From GSE6269 and GSE29161, respectively, a total of 201 and 741 DEGs were obtained. Gene Ontology (GO) analysis showed that CDEGs were primarily involved in innate immune response, extracellular exosome, as well as calcium ion binding, while the pathway analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed that CDEGs were significantly enriched in the B-cell receptor, IL-17, and NF-kappa B signaling pathways. The hub genes in the PPI network included HP, S100A12, SPI1, CD14, CCR1, S100A9 and so on. In the miRNA-TF-mRNA regulatory network, SPI1 could target miR-361-5p, miR-155-5p, and miR-339-5p in the progression of IE. CONCLUSIONS: Several pivotal genes and pathways were identified in the progression of S. aureus-induced IE, which may have the potential for early detection.