Identification of Marker Genes and Pathways in Patients with Primary Biliary Cholangitis

Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by cholestasis and cirrhosis, and in which hepatic failure may occur. This study explores the changes in the gene expression profiles of liver tissues during the pathogenesis of PBC. Array dataset GSE79850 was downloaded from the Gene Expression Omnibus database. GeneSpring software was used to analyze differentially expressed genes (DEGs) in liver tissues from PBC patients compared with those from controls. Gene ontology (GO) annotation, the Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome pathway enrichment analyses were performed by using Database for Annotation, Visualization and Integrated Discovery (DAVID) software. Cytoscape software was used to construct a protein-protein interaction (PPI) network. Plug-ins Molecular Complex Detection and iRegulon were used for clustering analysis and transcription factors related to key genes with PBC. A total of 77 DEGs, including 47 up- and 30 downregulated genes, were identified. The PPI network was established with 74 nodes and 356 protein pairs. The C-C motif chemokine ligand 5 (CCL5), interleukin 7 receptor (IL7R), and TNF receptor superfamily member 1A (TNFRSF1A) were identified as hub genes in the PPI network and may, therefore, be marker genes for PBC. Further, the upregulated genes CCL5 and IL7R, and downregulated TNFRSF1A were included in immune system processes as a GO term in the category Biological Processes. In conclusion, CCL5, IL7R, TNFRSF1A, and the immune response pathway may have crucial roles in PBC. These genes and pathways may be potential targets for treating PBC.