EMP1 as a Potential Biomarker in Liver Fibrosis: A Bioinformatics Analysis.

Abstract

Liver fibrosis is a wound-healing response to chronic injury, which may result in cirrhosis and liver failure. Studies have been carried on the mechanisms and pathogenesis of liver fibrosis. However, the potential cell-specific expressed marker genes involved in fibrotic processes remain unknown. In this study, we combined a publicly accessible single-cell transcriptome of human liver with microarray datasets to evaluate the cell-specific expression patterns of differentially expressed genes in the liver. We noticed that EMP1 (epithelial membrane protein 1) is significantly active not only in CCl₄ (carbon tetrachloride)-treated mouse liver fibrosis but also in BDL (bile duct ligation)-induced liver fibrosis and even in human fibrotic liver tissues such as alcoholic hepatitis, NASH (nonalcoholic steatohepatitis), and advanced stage liver fibrosis. Furthermore, we demonstrated that EMP1 is a specific fibrotic gene expressed in HSCs (hepatic stellate cells) and endothelial cells using the Protein Atlas single-cell transcriptome RNA-sequencing clustering. Its expression was significantly elevated in fibrotic HSCs or CCl₄ and NASH-induced fibroblasts. Previous research revealed that EMP1 plays a role in proliferation, migration, metastasis, and tumorigeneses in different cancers via a variety of mechanisms. Because HSC activation and proliferation are two important steps following liver injury, it would be interesting to investigate the role of EMP1 in these processes. All of this information suggested that EMP1 could be used as a novel fibrotic liver marker and a possible target in the future.