Analysis of the molecular mechanisms of ulcerative colitis and atherosclerosis by microarray data

Abstract

Adults can develop ulcerative colitis (UC), a chronic inflammatory illness of the colon, while atherosclerosis (AA) is a chronic inflammatory disease of the blood vessels caused by a range of risk factors. Prior research has demonstrated that UC increases the risk of AA, although the underlying pathological mechanisms are not entirely understood. The purpose of this work was to discover differentially expressed genes (DEGs) in UC and AA and investigate their molecular processes using a bioinformatics method. The UC (GSE36807) and AA (GSE28829) datasets were obtained from the Gene Expression Omnibus (GEO) database. Following the identification of genes that are differentially expressed in common with UC and AA, functional annotation, the construction of protein-protein interaction (PPI) networks and modules, the identification of hub genes, and co-expression analysis were carried out. A total of 105 (including 92 up-regulated and 13 down-regulated genes) DEGs were selected for correlation analysis in the above two datasets, and after Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional analysis immune responses, cytokines, and chemokines were found to play crucial roles in both diseases. Finally, a total of 16 hub genes were identified by CytoHubba and MCODE plugins in Cytoscape, including Chemokine (C-C motif) ligand 4(CCL4), Toll-like receptor 2 (TLR2), Integrin Beta 2(ITGB2), Chemokine (C-C motif) Receptor 1(CCR1), Toll-Like Receptor 8 (TLR8), Fc Fragment of IgG Receptor IIa (FCGR2A), Neutrophil Cytosolic Factor 2(NCF2), Leukocyte immunoglobulin-like receptor B2(LILRB2), FGR proto-oncogene, Src family tyrosine kinase(FGR), Intercellular Adhesion Molecule 1 (ICAM1), Caspase 1(CASP1), Matrix Metallopeptidase 9(MMP9), Cluster of Differentiation 163(CD163), Complement Component 5a Receptor 1 (C5AR1), Neutrophil Cytosolic Factor 4 (NCF4), Selectin P (SELP). This study discovered a link between UC and AA, as well as shared hub genes and pathways, which may bring new insights into the processes of UC and AA.

Keywords: Atherosclerosis; Bioinformatics; DEG’s; Hub genes; Ulcerative colitis.

Fig. 1

Research design flow chart.

Fig. 2

UC and AA datasets. The volcano plot and Venn diagram of differentially expressed genes (DEGs). (A) Volcano plot of DEGs in GSE36807. (B) Volcano plot of DEGs in GSE28829; Upregulated genes are marked in light red; downregulated genes are marked in light green. (C) Venn diagrams of the GSE36807 and GSE28829 datasets showing down-regulation of DEGs. (D) Venn diagrams of the GSE36807 and GSE28829 datasets showing upregulated expression of DEGs.

Fig. 3

Protein–protein interaction network and enrichment analysis of common DEGs. (A) PPI network diagram. Red indicates up-regulated genes, and green indicates down-regulated genes. (B,C) The enrichment analysis results of GO and KEGG Pathway. Adjusted P-value < 0.05 was considered significant.

Fig. 4

GO and KEGG pathway enrichment analysis of differentially expressed genes in ulcerative colitis and atherosclerosis. (A–C) Are three closely related sub-network gene clustering modules. (D,E) is an enrichment analysis of the modular genes GO and KEGG. The size of their circles indicates the number of genes and the horizontal coordinates indicate the frequency of participating genes in the total genes. Statistical significance is represented by p-values, p < 0.05 indicating significant enrichment.

Fig. 5

Co-expression analysis and functional enrichment of hub genes identified in UC and AA. (A) Upset plot showing 16 overlapping hub genes screened by six algorithms. (B) Analysis of Hub genes and their co-expressed genes by GeneMANIA. (C,D) GO and KEGG enrichment analysis of the hub genes. The outermost circle is term on the right and the inner circle on the left represents the significant p-value of the corresponding pathway of the gene.

Fig. 6

TFs regulatory network and their expression in GSE36807 and GSE28829. (A) retrotransposon regulation, yellow represents retrotransposons, red represents hub genes. (B,C) expression levels of retrotransposons in GSE36807 and GSE28829. Comparison of the two data sets was performed using the mean t-test. p-value < 0.05 suggests statistical significance. HC health control, UC ulcerative colitis, EA early atherosclerotic, AA atherosclerotic. *p < 0.05; **p < 0.01; ****p < 0.001.