SERPINB3 (formerly known as
squamous cell carcinoma antigen-1 or SCCA1) is a member of the family of
serine-protease inhibitors. SERPINB3 protects cells from oxidative stress conditions, but in chronic liver damage this
serpin may lead to
hepatocellular carcinoma through different strategies, including inhibition of apoptosis, induction of epithelial to mesenchymal transition and decrease of desmosomal junctions, cell proliferation and invasiveness. SERPINB3 may also contribute to
tumor cell resistance to anti-neoplastic drugs through its binding to the
respiratory Complex I, protecting cells from the
pro-oxidant action of chemotherapeutic agents. Mechanisms of
tumor growth promotion induced by SERPINB3 include the inhibition of intratumor infiltration of natural killer cells, up-regulation of Myc oncogene and the recent identification of this
serpin as a Ras-responsive factor. In the liver SERPINB3 and SERPINBB4
isoforms (known as
squamous cell carcinoma antigen or SCCA) are undetectable in normal hepatocytes, but their expression progressively increases in chronic
liver diseases, dysplastic nodules and
hepatocellular carcinoma. High SERPINB3 levels have been recently detected in HCC tissue of patients with early
tumor recurrence after surgical resection. In serum SERPINB3/4
isoforms (or SCCA) are detectable bound to IgMs (SCCA-
IgM) in the majority of HCV infected patients with HCC and in patients with
cirrhosis their levels and/or the progressive increase have been found correlated to the risk of HCC development. Preliminary findings in patients with HCC revealed that SCCA-
IgM was predictive of HCC prognosis, since low levels of this
biomarker were able to identify HCC patients with long overall and progression-free survival.