Abstract
Chronic hepatitis B virus (HBV) infection is a major risk factor for the development of hepatocellular carcinoma (HCC), the leading cause of cancer-related death worldwide. Despite progress in the prevention and therapy of HCC, high incidence and recurrence rates of HCC remain big threats, resulting in poor patient survival. Effective biomarkers and targets of HCC are therefore urgently needed for better management and to improve patient outcomes. Pre-S mutants have been well demonstrated as HBV oncoproteins that play important roles in HCC development through activation of multiple oncogenic signal pathways in hepatocytes, in vitro and in vivo. The presence of pre-S mutants in patients with chronic HBV infection and HBV-related HCC has been associated with a significantly higher risk of HCC development and recurrence after curative surgical resection, respectively. In this review, we summarize the roles of pre-S mutants as biomarkers for predicting HBV-related HCC development and recurrence, and highlight the pre-S mutants-activated oncogenic signal pathways as potential targets for preventing HBV-related HCC development.
Highlights
Hepatocellular carcinoma (HCC) is among the most prevalent human cancers, and the leading causes of cancer-related death worldwide [1,2]
We summarize the evidence that supports pre-S mutants as biomarkers for predicting and as targets for preventing the development and recurrence of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) (Table 1)
Shen et al performed similar analysis in another cohort of chronic HBV-infected patients, consistently showing that the prevalence of overall pre-S deletions in serum was as low as 7% at high replicative phase, but significantly increased to 13.9% and 37%, at intermediate and low replicative phases, respectively [32]
Summary
Hepatocellular carcinoma (HCC) is among the most prevalent human cancers, and the leading causes of cancer-related death worldwide [1,2]. Ground glass hepatocytes (GGHs) that harbor pre-S mutant proteins represent histologically preneoplastic lesions of HCC in patients with chronic HBV infection [14,15]. Two types of pre-S mutant proteins, the pre-S1 and pre-S2 mutants, are identified as the HBV large surface proteins that contain deletion mutations in the pre-S1 and pre-S2 gene segments, respectively [14,15] Both types of pre-S mutants have been well demonstrated as HBV oncoproteins, that can activate multiple oncogenic signal pathways to promote growth advantage of hepatocytes, eventually leading to HCC development in vitro and in vivo [15,16,17,18]. We summarize the evidence that supports pre-S mutants as biomarkers for predicting and as targets for preventing the development and recurrence of HBV-related HCC (Table 1)
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