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Zheng et al. Hepatoma Res 2018;4:17 Hepatoma Research
DOI: 10.20517/2394-5079.2018.08

Review Open Access

Pre-S2 and HBV associated hepatocellular
carcinoma

Ying Zheng, Yan-Yan Qian, Hong Fan

The Key Laboratory of Developmental Genes and Human Diseases, Department of Medical Genetics and Developmental
Biology, Medical School, Southeast University, Nanjing 210009, China.
Correspondence to: Prof. Hong Fan, The Key Laboratory of Developmental Genes and Human Diseases, Department of Medical
Genetics and Developmental Biology, Medical School, Southeast University, Dingjiaqiao #87, Nanjing 210009, China.
E-mail: fanh@seu.edu.cn
How to cite this article: Zheng Y, Qian YY, Fan H. Pre-S2 and HBV associated hepatocellular carcinoma. Hepatoma Res 2018;4:17.
http://dx.doi.org/10.20517/2394-5079.2018.08
Received: 24 Feb 2018 First Decision: 28 Mar 2018 Revised: 14 May 2018 Accepted: 14 May 2018 Published: 31 May 2018

Science Editor: Guang-Wen Cao Copy Editor: Guang-Zhe Zhu Production Editor: Cai-Hong Wang

Abstract
Hepatitis B virus (HBV) infection is a primary cause of hepatocellular carcinoma (HCC). Under selection pressures
of host immunity and/or immunoprophylaxis and antiviral therapies, HBV evolves by accumulating mutations in its
genome. Several studies highlighted the considerable importance of HBV surface (HBs) protein mutants (pre-S/S
variants) in tumorigenesis. Among those mutants, pre-S2 mutants have been recognized as “precursor lesions of HCC”
and as risk factors for post-operative recurrence of HCC. Pre-S2 mutants play important roles in tumor progression and
induce various mechanisms of tumorigenesis. These roles include that the cytoplasmic orientation of the pre-S2 domain
is essential for the transcriptional activator C-terminally truncated middle surface protein (MHBst) which participates
in the development of hepatocellular carcinoma. Pre-S2 mutants may also play important roles in HBV tumorigenesis by
inducing both endoplasmic reticulum stress-dependent and endoplasmic reticulum (ER) stress-independent pathways.
Because HCC has poor prognosis and its incidence is increasing, methods for the prevention and treatment of HCC
should be comprehensive. Emerging treatments based on ER stress may provide a new strategy.

Keywords: Pre-S2, hepatocellular carcinoma, hepatitis B virus, endoplasmic reticulum stress

INTRODUCTION
More than 240 million individuals worldwide are infected with chronic hepatitis B virus (HBV) . Chronic
[1]
HBV infection progresses to cirrhosis in up to 40% of untreated patients, and there is an associated risk
of decompensated cirrhosis and hepatocellular carcinoma . Several hypotheses have been proposed to
[2-6]

© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0
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