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. 2023 Sep;29(9):e13457.
doi: 10.1111/srt.13457.

Bioinformatics analysis to reveal the potential comorbidity mechanism in psoriasis and nonalcoholic steatohepatitis

Ningyi Xian  1 , Ruimin Bai  1 , Jiaqi Guo  1 , Ruiting Luo  1 , Hao Lei  1 , Bingqing Wang  2 , Yan Zheng  1
Affiliations

Bioinformatics analysis to reveal the potential comorbidity mechanism in psoriasis and nonalcoholic steatohepatitis

Ningyi Xian et al. Skin Res Technol. 2023 Sep.

Abstract

Purpose: An increasing amount of evidence suggests that psoriasis and nonalcoholic steatohepatitis (NASH) may occur simultaneously, whereas the underlying mechanisms remain unclear. Our research aims to explore the potential comorbidity mechanism in psoriasis and nonalcoholic steatohepatitis.

Materials and methods: The expression profiles of psoriasis (GSE30999, GSE13355) and NASH (GSE24807, GSE17470) were downloaded from GEO datasets. Next, common differently expressed genes (DEGs) of psoriasis and NASH were investigated. Then, GO and KEGG enrichment, protein interaction network (PPI) construction, and hub gene identification for DEGs were performed. Finally, immune cells expression, target genes predicted by common miRNAs, and transcription factors interaction analysis for hub genes were carried out.

Results: Twenty DEGs were identified in totally. GO analysis revealed response to the virus was the most enriched term, and hepatitis C and coronavirus disease-COVID-19 infection-associated pathways were mainly enriched in KEGG. A total of eight hub genes were collected, including IFIT1, IFIT3, OAS1, HPGDS, IFI27, IFI44, CXCL10, IRF9, and 11 TFs were predicted. Then, neutrophils and monocytes were identified as immune cells that express the most hub genes. Moreover, five common miRNAs for psoriasis and NASH and one common miRNAs (hsa-miR-1305)-mRNAs (CHL1, MBNL2) network were presented.

Conclusion: CHL1 and MBNL2 may participate in the process of psoriasis and NASH via regulating hsa-miR-1305, and together with eight hub genes may be potential therapeutic targets for future treatment for the co-occurrence of these two diseases. This comprehensive bioinformatic analysis provides new insights on molecular pathogenesis and identification of potential therapeutic targets for the co-occurrence of them.

Keywords: bioinformatics; differentially expressed genes; microRNAs (miRNAs); nonalcoholic steatohepatitis; psoriasis.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

FIGURE 1
FIGURE 1
The flowchart of this study.
FIGURE 2
FIGURE 2
Volcano map of GSE30999, GSE13355, GSE24807, and GSE17470 and Venn diagram of common DEGs. (A) The volcano map of GSE30999. (B) The volcano map of GSE13355. (C) The volcano map of GSE24807. (D) The volcano map of GSE17470. Red represents upregulated genes, and blue represents downregulated genes. (E) The four datasets have an overlap of four common downregulated genes. (F) The four datasets have an overlap of 16 common upregulated genes.
FIGURE 3
FIGURE 3
Enrichment analysis and PPI network of common DEGs. (A) Enrichment analysis of common DEGs is shown with bar chart in BP, MF, and KEGG. (B) Enrichment analysis of common DEGs is shown with bubble diagram. (C) Enrichment analysis of common DEGs is shown with network planning. (D) PPI network of common DEGs contains 15 nodes and 31 interactions. (E) Eight hub genes are selected from PPI network. Orange represents upregulated genes, and blue represents downregulated genes.
FIGURE 4
FIGURE 4
Identification and analysis of hub genes. (A) Hub genes and their co‐expression genes network. (B) Enrichment analysis of hub genes is shown with bar chart in BP, CC, MF, and KEGG. (C) Enrichment analysis of hub genes is shown with bubble diagram. (D) Enrichment analysis of hub genes is shown with network planning.
FIGURE 5
FIGURE 5
Exploration of hub genes in immune cells. (A–H) Eight bar charts showing expression of each hub gene in immune cells in decreasing order.
FIGURE 5
FIGURE 5
Exploration of hub genes in immune cells. (A–H) Eight bar charts showing expression of each hub gene in immune cells in decreasing order.
FIGURE 6
FIGURE 6
Exploration of hub genes with their neighbor genes and their transcription factors. (A) The network of hub genes and their nearest neighbors. Orange represents hub genes and yellow represents their neighbors based on immune cell RNA expression. (B) Regulatory network of TFs. Orange represents related hub genes, and blue represents TFs.
FIGURE 7
FIGURE 7
Exploration of miRNAs. (A) Five overlapping miRNA in psoriasis and psoriasis. (B) Cell specificity of common miRNAs, top seven are shown. (C) Function of common miRNAs via heat map. (D) Function of common miRNAs via bar plot, top nine are shown. (E) Two overlapping genes between target genes of miRNAs and common DEGs. (F) The miRNAs‐mRNAs network. Blue represents miRNAs and yellow represents common DEGs.
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