Identification of serum ß-catenin as a biomarker in patients with HBV-related liver diseases.

ABSTRACT

BACKGROUND: Substantial evidence indicates that ß-catenin is a pivotal regulator that contributes to the initiation and development of various types of diseases. Recently, ß-catenin can be detected in human serum and also reported to be correlated with several disease progression in a little research. However, very little is known about the relationship between serum ß-catenin and HBV-related liver disease. METHODS: Serum levels of ß-catenin, from 77 patients with chronic hepatitis B (CHB), 63 patients with hepatitis B associated liver cirrhosis (HBLC), 61 patients with hepatocellular carcinoma (HCC), 41 healthy HBV carriers (HHCs) and 78 healthy controls (HCs) were measured by ELISA. Correlations of serum ß-catenin with viral replication and liver necroinflammation parameters were analyzed. The receiver operating characteristic (ROC) curve was used to assess the discriminating power of serum ß-catenin to grade different stages of HBV-related disorders. Human hepatic cell line L02 was transfected with a HBV plasmid, and ß-catenin levels and the underlying mechanism were analyzed. RESULTS: Chronic hepatitis B and HBLC patients but not HHC or HCC showed significantly higher serum ß-catenin levels than HCs. ß-catenin levels were not correlated with HBV DNA levels but were correlated with necroinflammation parameters. HBV-infected cell model showed elevated levels of phosphorylation at Ser473 in Akt (p-Akt), phosphorylation at Ser9 in GSK3ß (p-GSK3ß) and ß-catenin, all of which was blocked by treatment with Akt inhibitor LY294002. Additionally, ROC analysis of ß-catenin for discriminating patients with CHB from HHCs, which yielded an AUC of 0.71 (cutoff value, 42 pg/mL; 95% CI 0.61-0.81) with 64.93% sensitivity, 73.17% specificity and 69.05% accuracy. ROC analysis of ß-catenin for discriminating patients with HCC from chronic HBV infection mainly including CHB and HBLC, which yielded an AUC of 0.75 (cutoff value, 42 pg/mL; 95% CI 0.67-0.83) with 66.43% sensitivity, 75.41% specificity and 70.92% accuracy. CONCLUSIONS: HBV infection enhances ß-catenin expression by activating Akt/GSK3ß signaling. Serum ß-catenin levels are correlated with necroinflammation parameters but not with viral load. Serum ß-catenin has potential to discriminate the phase of HBV-related disorders, particularly predicts the patients with CHB from HHCs and also predicting HCC form chronic HBV infection.