The impact of serpinB3-PD polymorphism on the prognosis of patients with hepatocellular carcinoma

Pietro Guerra; Mariagrazia Ruvoletto; Santina Quarta; Giulia Boninsegna; Alessandra Biasiolo; Silvia Cagnin; Paolo Angeli; Patrizia Pontisso; Andrea Martini

doi:10.1016/j.tranon.2025.102413

The impact of serpinB3-PD polymorphism on the prognosis of patients with hepatocellular carcinoma

Transl Oncol. 2025 Jul:57:102413. doi: 10.1016/j.tranon.2025.102413. Epub 2025 May 13.

Authors

Pietro Guerra¹, Mariagrazia Ruvoletto², Santina Quarta², Giulia Boninsegna¹, Alessandra Biasiolo², Silvia Cagnin¹, Paolo Angeli², Patrizia Pontisso², Andrea Martini³

Affiliations

¹ Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, via Giustiniani, 2, 35128, Padova, Italy.
² Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, via Giustiniani, 2, 35128, Padova, Italy; European Reference Network - ERN RARELIVER, Department of Medicine, Azienda Ospedale-Università, Padova, Italy.
³ Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, via Giustiniani, 2, 35128, Padova, Italy; European Reference Network - ERN RARELIVER, Department of Medicine, Azienda Ospedale-Università, Padova, Italy. Electronic address: andrea.martini@aopd.veneto.it.

Abstract

Background: HCC ranks as the third leading cause of cancer-related death, yet current surveillance strategies miss over one-third of cases at an early stage. SerpinB3-PD (SB3-PD), a polymorphic isoform of a serine-protease inhibitor involved in tumorigenesis and fibrogenesis, has been related to a more rapid cirrhosis decompensation. This study investigates the prognostic role of SB3-PD in patients with HCC.

Methods: SB3-PD polymorphism was assessed in 140 patients with HCC, followed up in our outpatient Clinic. Cell invasion analysis was conducted on HepG2 cells either overexpressing the SB3 wild-type (HepG2/SB3WT) or the PD isoform (HepG2/SB3PD). The effect of recombinant SB3-WT or SB3-PD on the production of molecules that impair immunosurveillance was also assessed in the THP-1 monocytic cell line.

Results: Patients carrying SB3-PD polymorphism showed worse tumour characteristics, associated with significantly lower survival and SB3-PD was an independent predictor of mortality. HepG2/SB3PD cells had a significantly higher invasion capacity than the HepG2/SB3WT. In THP-1 cells recombinant SB3-PD induced higher levels of PDL1 and IL-13 than SB3-WT.

Conclusion: SB3-PD isoform is associated with worse clinical prognosis in patients with HCC. These findings were supported in vitro by increased cellular invasion and higher production of molecules impairing immunosurveillance.

Keywords: Hepatocellular carcinoma; Polymorphism; Prognosis; SerpinB3.