Identifying differentially expressed genes and miRNAs in Kawasaki disease by bioinformatics analysis

Abstract

AbstractKawasaki disease (KD) is an acute systemic immune vasculitis caused by infection, and its etiology and underlying mechanisms are not completely clear. This study aimed to identify differentially expressed genes (DEGs) with diagnostic and treatment potential for KD using bioinformatics analysis. In this study, three KD datasets (GSE68004, GSE73461, GSE18606) were downloaded from the Gene Expression Omnibus (GEO) database. Identification of DEGs between normal and KD whole blood was performed using the GEO2R online tool. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis of DEGs was undertaken with Metascape. Analysis and visualization of protein–protein interaction networks (PPI) were carried out with STRING and Cytoscape. Lastly, miRNA-genes regulatory networks were built by Cytoscape to predict the underlying microRNAs (miRNAs) associated with DEGs. Overall, 269 DEGs were identified, including 230 up-regulated and 39 down-regulated genes. The enrichment functions and pathways of DEGs involve regulation of defense response, inflammatory response, response to bacterium, and T cell differentiation. KEGG analysis indicates that the genes were significantly enriched in Neutrophil extracellular trap formation, TNF signaling pathway, Cytokine-cytokine receptor interaction, and Primary immunodeficiency. After combining the results of the protein–protein interaction (PPI) network and CytoHubba, 9 hub genes were selected, including TLR8, ITGAX, HCK, LILRB2, IL1B, FCGR2A, S100A12, SPI1, and CD8A. Based on the DEGs-miRNAs network construction, 3 miRNAs including mir-126-3p, mir-375 and mir-146a-5p were determined to be potential key miRNAs. To summarize, a total of 269 DEGs, 9 hub genes and 3 miRNAs were identified, which could be considered as KD biomarkers. However, further studies are needed to clarify the biological roles of these genes in KD.