Integrative proteomics and transcriptomics identify novel fibrosis-related biomarkers of patients with post-HBV hepatitis cirrhosis

Background: Hepatitis B virus (HBV) infection is an important public health burden. Chronic HBV infection always leads to chronic hepatitis, liver fibrosis and increases the incidence of liver cancer. However, the mechanism of liver fibrosis caused by persistent HBV infection remains unclear. Methods: In present study, we isolated and enriched primary human hepatic stellate cells (HSCs) from chronically HBV infected patients with liver cirrhosis. The differences expression of mRNA and protein were analyzed by combining proteomics, transcriptomics, and biological network analysis. Results: After bioinformatics analysis with transcriptomics and proteomics data, a total of 2,156 genes and 711 proteins were differently expressed between the liver cirrhosis group and control group. GO enrichment analysis and KEGG analysis indicated those differently expressed molecules were mainly involved in oxidative stress, glycometabolism, and fibrous repair. Moreover, a total of 110 overlapping biomarker were identified and two of them (PKM2 and EHD2) were validated as candidates correlated with liver fibrosis by qRT-PCR and immunofluorescence from primary human HSCs and in vitro cellular hepatic fibrosis model. Conclusion: Our results indicated that PKM2 and EHD2 were overexpressed in chronically HBV infected patients with liver cirrhosis, suggesting them as potential biomarkers and therapeutic targets for liver fibrosis.