Transcriptomic Analysis of Hepatitis B Infected Liver for Prediction of Hepatocellular Carcinoma

SIMPLE SUMMARY: Hepatitis B virus infection increases the risk of developing liver cancer, a common health problem worldwide. In this study, we aimed to identify patients with hepatitis B infection who have a higher risk of cancer development. Our results reveal that liver tissues from hepatitis B patients can be clearly classified according to whether they express higher levels of messenger RNA produced from a panel of genes related to proliferation and inflammation. A subgroup of genes in this panel are linked to cancer development and shorter lifetimes in liver cancer patients. The new gene list we define here has the potential to be used as a new approach for the molecular identification of patients with hepatitis-B-virus-infected livers and who are at risk of liver cancer development. ABSTRACT: Hepatocellular cancer (HCC) is a leading cause of cancer-related mortality worldwide, and chronic hepatitis B virus infection (CHB) has been a major risk factor for HCC development. The pathogenesis of HBV-related HCC has been a major focus revealing the interplay of a multitude of intracellular signaling pathways, yet the precise mechanisms and their implementations to clinical practice remain to be elucidated. This study utilizes publicly available transcriptomic data from the livers of CHB patients in order to identify a population with a higher risk of malignant transformation. We report the identification of a novel list of genes (PCM1) which can generate clear transcriptomic sub-groups among HBV-infected livers. PCM1 includes genes related to cell cycle activity and liver cancer development. In addition, markers of inflammation, M1 macrophages and gamma delta T cell infiltration are present within the signature. Genes within PCM1 are also able to differentiate HCC from normal liver, and some genes within the signature are associated with poor prognosis of HCC at the mRNA level. The analysis of the immunohistochemical stainings validated that proteins coded by a group of PCM1 genes were overexpressed in liver cancer, while minimal or no expression was detected in normal liver. Altogether, our findings suggest that PCM1 can be developed into a clinically applicable method to identify CHB patients with a higher risk of HCC development.