Impact of E-cadherin and its transcription regulators on assessing epithelial-mesenchymal transition in chronic HCV infection.

Abstract

BACKGROUND The mechanisms of chronic hepatitis C virus (HCV)-induced liver fibrosis and hepatocarcinogenesis are still poorly recognized. Therefore, this study aimed to determine the effect of chronic HCV infection on the expression of the major regulators of epithelialmesenchymal transition (EMT) including E-cadherin, snail, slug, and twist2, in the Egyptian population. This will help to design more efficient strategies to treat HCV-associated cirrhosis and carcinoma. METHODS Fifty-nine liver biopsies from patients, that were serologically proven to be HCV positive, were included in the current study. Histopathological examination was done. Grading of hepatitis activity (A) and staging of fibrosis (F) were assessed using the METAVIR scoring system. Additionally, an immunohistochemical examination of E-cadherin, snail, slug, and twist2 expression was performed. RESULTS E-cadherin showed a significant progressive decline of its expression with increased fibrosis staging and development of hepatocellular carcinoma (HCC). In contrast, snail and slug expression was positively associated with the stage of fibrosis and HCC. Meanwhile, twist2 expression wasn't affected by the degree of hepatitis activity, the stage of fibrosis, or by the development of HCC. CONCLUSIONS E-cadherin and its transcriptional regulators; snail and slug may serve as indicators for assessing the stage of fibrosis and the progression of HCC associated with HCV infection but not for assessing the degree of hepatitis activity. Therefore, the snail family could be a promising target for designing effective preventive and therapeutic strategies for chronic HCV infection and its serious co-morbidities.