Dissection of the Molecular and Immunological Interaction in Patients With Hepatocellular Carcinoma of Viral and Non-viral Etiologies

This study will start with a "training cohort" of the NTUH and NTU Cancer Center patients, consisting of 4 sub-groups: HBV (+) steatosis (+), HBV (-) steatosis (+), HBV (+) steatosis (-) and HBV (-) steatosis (-). HBV (+) is defined as either: (a) HBsAg (+) or (b) HBsAg (-) anti-HBc (+) and HBV DNA detectable in blood or tumor tissue. Steatosis is defined by histology. We will enroll 400 patients who had sufficient tissue for testing in the training cohort. The following studies will be performed: (1) NGS of targeted genes panel using the National Health Research Institutes precision medicine platform; (2) transcriptomic analysis of immune microenvironment using RNA-seq and multiplex immunofluorescence staining; (3) lipotoxic genotyping for SNPs; (4) clinical outcomes of MAFLD vs. non-MAFLD. The genetic and immunological features will be further tested by a "validation cohort", from collaborative hospitals. This project will clarify the potential interaction between HBV infection and steatosis, and their impact on genetic alterations and tumor immune microenvironment.