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.
The impact of serpinB3-PD polymorphism on the prognosis of patients with hepatocellular carcinoma
Guerra P.;Ruvoletto M.;Quarta S.;Biasiolo A.;Cagnin S.;Pontisso P.;Martini A.
2025
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.
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