Bioinformatics based analysis of the underlying comorbidity mechanisms of non-alcoholic steatohepatitis and primary biliary cholangitis

Abstract

Abstract Objective To identify the common key genes and potential comorbidity mechanisms in the progression of non-alcoholic steatohepatitis (NASH) and primary biliary cholangitis (PBC) by bioinformatics technology. Methods The NASH and PBC chip datasets were downloaded from GEO database, common differentially expressed genes (co-DEGs) were screened and studied by Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG)and Gene Set Enrichment Analysis (GSEA). The protein-protein interaction network (PPI) was constructed, hub genes and target miRNAs and transcription factors (TFs) were screened. ROC curve was used to evaluate the diagnostic value of hub genes. Finally, immune infiltration analysisand the relationship between immune cells and hub genes were performed by CIBERSORT algorithm. Results There were a total of 25 comorbid genes between NASH and PBC. They were mainly involved in cytokine-mediated signaling pathway, granulocyte chemotaxis and migration, inflammatory response and lipid metabolic process. A total of 9 hub genes were screened, among them TNFRSF1A, CXCL2, IL-1RAP were the key comorbid genes, hsa-miR-141-3p, hsa-miR-335-5p were among the key comorbid miRNAs, CEBPA, CEBPB were the key TFs. All these hub genes had good diagnostic value. Immune infiltration analysis demonstrated that M1 macrophage occupies an important position and positively correlated with CXCL9. Conclusion Inflammation cytokines, macrophages and inflammatory responses play important roles in the progression of NASH and PBC. The hub genes screened in our study might become diagnostic markers and potential therapeutic targets, while further basic and clinical studies are needed to validate.