Abstract
Background: Ulcerative colitis (UC) is a chronic, complicated, inflammatory disease with an increasing incidence and prevalence worldwide. However, the intrinsic molecular mechanisms underlying the pathogenesis of UC have not yet been fully elucidated.Methods: All UC datasets published in the GEO database were analyzed and summarized. Subsequently, the robust rank aggregation (RRA) method was used to identify differentially expressed genes (DEGs) between UC patients and controls. Gene functional annotation and PPI network analysis were performed to illustrate the potential functions of the DEGs. Some important functional modules from the protein-protein interaction (PPI) network were identified by molecular complex detection (MCODE), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG), and analyses were performed. The results of CytoHubba, a plug for integrated algorithm for biomolecular interaction networks combined with RRA analysis, were used to identify the hub genes. Finally, a mouse model of UC was established by dextran sulfate sodium salt (DSS) solution to verify the expression of hub genes.Results: A total of 6 datasets met the inclusion criteria (GSE38713, GSE59071, GSE73661, GSE75214, GSE87466, GSE92415). The RRA integrated analysis revealed 208 significant DEGs (132 upregulated genes and 76 downregulated genes). After constructing the PPI network by MCODE plug, modules with the top three scores were listed. The CytoHubba app and RRA identified six hub genes: LCN2, CXCL1, MMP3, IDO1, MMP1, and S100A8. We found through enrichment analysis that these functional modules and hub genes were mainly related to cytokine secretion, immune response, and cancer progression. With the mouse model, we found that the expression of all six hub genes in the UC group was higher than that in the control group (P < 0.05).Conclusion: The hub genes analyzed by the RRA method are highly reliable. These findings improve the understanding of the molecular mechanisms in UC pathogenesis.
Highlights
MATERIALS AND METHODSUlcerative colitis (UC) is a chronic, complicated, inflammatory disease that affects the colonic mucosa and most commonly presents with abdominal pain, diarrhea, and blood in the stools
Some important functional modules from the protein-protein interaction (PPI) network were identified by molecular complex detection (MCODE), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG), and analyses were performed
We found that the expression of all six hub genes in the UC group was higher than that in the control group (P < 0.05)
Summary
Ulcerative colitis (UC) is a chronic, complicated, inflammatory disease that affects the colonic mucosa and most commonly presents with abdominal pain, diarrhea, and blood in the stools. The incidence and prevalence of UC have been increasing worldwide. It usually has a long, chronic clinical course, and UC patients are at increased risk of colorectal cancer. It is believed that multifactorial pathogenesis plays a role in the occurrence and development of UC, and the factors involved include environmental and psychological factors, dysregulated intestinal flora and immune responses, genetic predisposition, and epithelial barrier defects. Breakdown of the epithelial barrier is underlying in UC pathogenesis (Ungaro et al, 2017; Parikh et al, 2019). Ulcerative colitis (UC) is a chronic, complicated, inflammatory disease with an increasing incidence and prevalence worldwide. The intrinsic molecular mechanisms underlying the pathogenesis of UC have not yet been fully elucidated
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