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. 2022 Dec 19;12(1):21879.
doi: 10.1038/s41598-022-26608-x.

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

Yanliang Cai #  1 , Weitao Hu #  2
Affiliations

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

Yanliang Cai et al. Sci Rep. .

Abstract

Kawasaki 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.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Volcano plots showing differentially expressed genes (DEGs) between the control and KD groups. (A–C) DEGs of the GSE68004, GSE73461 and GSE18606 datasets are shown, respectively. Red data points indicate up-regulated genes and blue ones indicate down-regulated genes. Genes without any significant differences are in black.
Figure 2
Figure 2
Venn diagram displaying the overlapping differentially expressed genes (DEGs) in three datasets searched from Gene Expression Omnibus (GEO). (A, B) illustrate the overlap of up-regulated and down-regulated genes in the GSE68004, GSE73461 and GSE18606 datasets, respectively.
Figure 3
Figure 3
Functional enrichment of DEGs. Bar graphs display the results of the top 20 enrichment analyses for up-regulated genes (A, C) and down-regulated genes (B, D). P-value is shown in color.
Figure 4
Figure 4
Network construction and module analysis. (A) Construction of a protein–protein interaction network using Cytoscape. The network includes 269 nodes and 869 edges. 2 edges between nodes indicate gene–gene interactions. The node corresponding to each gene is sized and colored according to the degree of interaction. The color scale indicates the change in the degree of each gene from high (blue) to low (white). Closer to the blue node, the higher the degree of connectivity between the 2 nodes. (B) The most densely connected region of the PPI network (16 nodes, 64 edges) was identified using MCODE. (C) 9 hub genes were determined in the densest connected region using the 8 algorithms in cytoHubba. The degree scores are represented in pink color. A darker color means a higher degree score.
Figure 5
Figure 5
Functional enrichment of hub genes (A) Bar graph of GO analyses of hub genes. P-values were indicated by color. The network of enriched terms of hub genes; colors indicated the same cluster-ID (B) and P-value (C).
Figure 6
Figure 6
Validation of hub genes in the GSE73461 dataset. (A) ROC analysis of hub genes in KD. Different genes are indicated by different colors. (B) Box plot depicting the expression of hub genes in KD and normal samples.
Figure 7
Figure 7
Validation of hub genes in the GSE68004 dataset. (A) ROC analysis of hub genes in KD. Different genes are indicated by different colors. (B) Box plot depicting the expression of hub genes in KD and normal samples.
Figure 8
Figure 8
Validation of hub genes in the GSE18606 dataset. (A) ROC analysis of hub genes in KD. Different genes are indicated by different colors. (B) Box plot depicting the expression of hub genes in KD and normal samples.
Figure 9
Figure 9
Network of integrated miRNA-DEGs with 8 hub genes. Green diamonds indicate the 8 hub genes. Gray circles indicate miRNAs with low connection to the hub genes. Dark pink octagons indicate miRNAs with high connection to the hub genes.
Figure 10
Figure 10
Hub genes and miRNAs in KD.
See this image and copyright information in PMC

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