Identification of PBK as a Novel Regulator of HBV-HCC
Chronic HBV infection is a well-established etiological factor for HCC. HBV exerts its oncogenic potential primarily through integration of its DNA into the host genome and expression of viral proteins, such as HBx. While previous studies have identified numerous genes involved in HCC progression, relatively few have elucidated host factors connecting HBV replication and liver carcinogenesis. To fill this knowledge gap, we performed RNA-seq analysis on tumor, adjacent, and background liver tissues from chronic HBV-infected patients with HCC. Our integrative analysis identified PBK (PDZ-binding kinase) as the only significantly upregulated gene consistently observed across our cohort, TCGA-LIHC, and GSE94660 datasets. PBK, also known as TOPK, is related to the MAPKK family and functions as an upstream activator of p38, contributing to the cellular response to DNA damage. In this study, we investigated the biological function of PBK in both HCC progression and HBV replication and identified it as a key molecular link between viral infection and tumor biology in the context of HBV-HCC.