Abstract
Hepatitis B is the most prevalent viral hepatitis worldwide, affecting approximately one-third of the world’s population. Among HBV factors, the surface protein is the most sensitive biomarker for viral infection, given that it is expressed at high levels in all viral infection phases. The large HBV surface protein (LHBs) contains the integral pre-S1 domain, which binds to the HBV receptor sodium taurocholate co transporting polypeptide on the hepatocyte to facilitate viral entry. The accumulation of viral LHBs and its prevalent pre-S mutants in chronic HBV carriers triggers a sustained endoplasmic reticulum (ER) overload response, leading to ER stress-mediated cell proliferation, metabolic switching and genomic instability, which are associated with pro-oncogenic effects. Ground glass hepatocytes identified in HBV-related hepatocellular carcinoma (HCC) patients harbor pre-S deletion variants that largely accumulate in the ER lumen due to mutation-induced protein misfolding and are associated with increased risks of cancer recurrence and metastasis. Moreover, in contrast to the major HBs, which is decreased in tumors to a greater extent than it is in peritumorous regions, LHBs is continuously expressed during tumorigenesis, indicating that LHBs serves as a promising biomarker for HCC in people with CHB. Continuing efforts to delineate the molecular mechanisms by which LHBs regulates pathological changes in CHB patients are important for establishing a correlation between LHBs biomarkers and HCC development.
Highlights
Chronic hepatitis B (CHB) virus infection is the most important cause of hepatocellular carcinoma (HCC) worldwide
Signaling pathway causes the sterol regulatory element binding transcription factor 1 (SREBF1)-induced upregulation of ATP citrate lyase (ACLY) and fatty acid desaturase 2 (FADS2), leading to an increase in triglycerides and cholesterol [77]. These findings clearly indicate that large HBV surface protein (LHBs)-induced endoplasmic reticulum (ER) stress-mediated lipid metabolism disturbance is functionally linked to HBV tumorigenesis
A later study by Wang et al [46] showed that ground glass hepatocytes (GGHs) harbor pre-S deletion variants that accumulate in the ER and induce ER stress signaling
Summary
Chronic hepatitis B (CHB) virus infection is the most important cause of hepatocellular carcinoma (HCC) worldwide. 2 billion people, has been infected with HBV, and more than 200 million people suffer from CHB [1]. Individuals with CHB are at a greater than 100-fold increased risk of developing advanced liver diseases, including cirrhosis and HCC [2,3]. HCC remains among the leading causes of cancer death worldwide. Effective prevention and control of HBV infection are very important public health issues in countries with epidemic HBV. In some regions, such as South Korea, Singapore and Taiwan, where the nationwide HBV vaccination of newborns has been executed for a few decades, Cells 2020, 9, 2052; doi:10.3390/cells9092052 www.mdpi.com/journal/cells
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
