THE ROLE OF THE HEPATITIS B VIRUS IN THE DEVELOPMENT OF HELATOCELLULAR CARCINOMA

Abstract

The Hepatitis B virus (HBV) has been strongly implicated in HBV associated Hepatocellular Carcinoma (HCC) in South East Asia, where genotype B of HBV is predominantly found. There is an urgent need to understand HCC tumorigenesis for better treatment and management due to the limited treatment option and late detection of this disease. Deep analytics was performed on >9,000 existing publications to gain a deeper understanding of the current state of HBV-HCC research, with an important network of 143 molecules that has 14 nodal, and targetable molecules important in HCC tumorigenesis. RNA-sequencing on local HBV-HCC patients identified 110 candidate genes to be correlated with important patient clinical phenotypes like survival, vascular invasion and Edmonson’s grading of tumors. Functional characterization of HBx, a HBV gene frequently integrated into the host, revealed that genotype B HBx ¬plays a pronounced role in metastatic related functions, while Chimeric variants of HBx expressed in HCC patients exhibited a more tumorigenic role in HCC development. Put together, this thesis created a platform for analytics on existing literature, identified candidate genes for biomarker development and elucidated the roles of HBxB and its variants in HCC development.