Bioinformatics Analysis Reveals shared molecular pathways for Relationship between Ulcerative Colitis and Primary Sclerosing Cholangitis

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 extra-intestinal organs, which may manifest prior to the diagnosis of IBD. Among these extra-intestinal 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. Aim of the study: In this study, we 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 We conducted a comprehensive bioinformatics analysis to detect UC and PSC-associated genes. The common differentially expressed genes (DEGs) and common single nucleotide polymorphisms (SNPs) were detected using the GEO and DisGeNET 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. At last, we searched the DGIdb database for possible interacting drugs with UC-PSC top module genes. Results Our microarray dataset analysis identified 56 common DEGs between UC and PSC with significant enrichment in genes involved in mRNA processes such as mRNA splicing process, and RNA bindings. We also identified 291 common DEGs from the DisGeNET database, demonstrating only one common DEG, called PTPN2, with microarray dataset. In this study we also identified 122 common SNPs between UC and PSC. Additionally, the top cluster of PPI network analysis was consisted of PABPC1, SNRPA1, NOP56, NHP2L1, and HNRNPA2B1 genes. We constructed a ceRNA network involving 4 specific mRNAs, 94 miRNAs, and 200 selected circRNAs. Conclusion In 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.