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Martini et al. Hepatoma Res 2018;4:28 Hepatoma Research
DOI: 10.20517/2394-5079.2018.50

Review Open Access

Pro-oncogenic role of SerpinB3 in hepatocellular
carcinoma

Andrea Martini, Patrizia Pontisso

Department of Medicine, University of Padua, Padua 35128, Italy.
Correspondence to: Prof. Patrizia Pontisso, Department of Medicine, University of Padua, Via Giustiniani 2, Padua 35128, Italy.
E-mail: patrizia@unipd.it

How to cite this article: Martini A, Pontisso P. Pro-oncogenic role of SerpinB3 in hepatocellular carcinoma. Hepatoma Res
2018;4:28. http://dx.doi.org/10.20517/2394-5079.2018.50

Received: 4 May 2018 First Decision: 22 May 2018 Revised: 6 Jun 2018 Accepted: 7 Jun 2018 Published: 29 Jun 2018
Science Editor: Guang-Wen Cao Copy Editor: Jun-Yao Li Production Editor: Cai-Hong Wang

Abstract
Hepatocellular carcinoma (HCC) is one of the most relevant sanitary problems for its prevalence and poor prognosis.
This tumor is characterized by highly heterogeneous features, both at clinical and molecular level. SerpinB3 (squamous
cell carcinoma antigen-1 or SCCA1) is a serine-protease inhibitor that protects cells from oxidative stress conditions,
but in chronic liver damage it may lead to HCC through different strategies, including inhibition of apoptosis, induction
of epithelial to mesenchymal transition, cell proliferation and invasiveness. Mechanisms of tumor growth promotion
induced by SerpinB3 encompass the inhibition of intratumor infiltration of natural killer cells and the up-regulation of Myc
oncogene. Recently this serpin has also been identified as a Ras-responsive factor and modulator of metabolic pathways.
In the liver SerpinB3 is undetectable in normal hepatocytes, but its expression progressively increases in chronic liver
diseases, dysplastic nodules and hepatocellular carcinoma, especially in those with poor prognosis, in which it could
also exert immunomodulatory effects. In serum SerpinB3/4 isoforms (or SCCA) circulate bound to IgMs (SCCA-IgM) in
patients with HCC, and in patients with cirrhosis their levels have been found correlated to the risk of HCC development.
Preliminary findings in patients with HCC revealed that SCCA-IgM levels are predictive of HCC prognosis.

Keywords: SerpinB3, chronic liver disease, hepatocellular carcinoma, chronic inflammation, SCCA-IgM

INTRODUCTION
Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and is ranked as the sixth most
common neoplasm and the third leading cause of cancer death worldwide. This liver tumor has been recognised
as a leading cause of death among patients with cirrhosis and its incidence is expected to increase in the next

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