Bioinformatics analysis reveals shared molecular pathways for relationship between ulcerative colitis and primary sclerosing cholangitis.

Abstract

Background: Inflammatory bowel disease (IBD) is a group of chronic inflammatory disorders, including ulcerative colitis (UC) and Crohn's disease, affecting the gastrointestinal tract and is associated with high morbidity and mortality. Accumulating evidence indicates that IBD not only impacts the gastrointestinal tract but also affects multiple extraintestinal organs, which may manifest prior to the diagnosis of IBD. Among these extraintestinal manifestations associated with IBD, primary sclerosing cholangitis (PSC) stands out as a prominent example. PSC is recognized as a progressive cholestatic disorder, characterized by the narrowing of bile ducts, eventual development of liver cirrhosis, end-stage liver disease, and the potential emergence of cholangiocarcinoma. This study aimed to identify the molecular contributors in UC-induced PSC by detecting the essential regulatory genes that are differentially expressed in both diseases.

Materials and methods: The common single-nucleotide polymorphisms (SNPs) and differentially expressed genes (DEGs) were detected using DisGeNET and GEO databases, respectively. Then, the top module and hub genes within the protein-protein interaction network were identified. Furthermore, the co-expression network of the top module was constructed using the HIPPIE database. Additionally, the gene regulatory network was constructed based on miRNAs and circRNAs. Finally, we searched the DGIdb database for possible interacting drugs with UC-PSC top module genes.

Results: A total of 132 SNPs and their associated genes were found to be shared between UC and PSC. Gene expression analysis identified 56 common DEGs between the two diseases. Following functional enrichment analysis, 207 significant biological processes (BP), 48 molecular functions (MF), and 8 KEGG pathways, with notable enrichment in mRNA-related processes such as mRNA splicing and RNA binding, were defined. Particularly, the PTPN2 gene was the only gene common between UC and PSC at both the SNP level and the expression level. Additionally, the top cluster of PPI network analysis was consisted of PABPC1, SNRPA1, NOP56, NHP2L1, and HNRNPA2B1 genes. Finally, ceRNA network involving 4 mRNAs, 94 miRNAs, and 200 selected circRNAs was constructed.

Conclusion: The present study provides novel potential candidate genes that may be involved in the molecular association between ulcerative colitis and primary sclerosing cholangitis, resulting in the development of diagnostic tools and therapeutic targets to prevent the progression of PSC from UC.