Guerra Pietro, Ruvoletto Mariagrazia, Quarta Santina, Boninsegna Giulia, Biasiolo Alessandra, Cagnin Silvia, Angeli Paolo, Pontisso Patrizia, Martini Andrea
Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, via Giustiniani, 2, 35128, Padova, Italy.
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.
Transl Oncol. 2025 Jul;57:102413. doi: 10.1016/j.tranon.2025.102413. Epub 2025 May 13.
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.
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.
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.
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.
肝癌是癌症相关死亡的第三大主要原因，但目前的监测策略会遗漏超过三分之一的早期病例。丝氨酸蛋白酶抑制剂的一种多态性异构体SerpinB3-PD（SB3-PD）参与肿瘤发生和纤维生成，与肝硬化更快失代偿有关。本研究调查SB3-PD在肝癌患者中的预后作用。
对140例肝癌患者进行SB3-PD多态性评估，并在我们的门诊诊所进行随访。对过表达SB3野生型（HepG2/SB3WT）或PD异构体（HepG2/SB3PD）的HepG2细胞进行细胞侵袭分析。还在THP-1单核细胞系中评估重组SB3-WT或SB3-PD对损害免疫监视的分子产生的影响。
携带SB3-PD多态性的患者表现出更差的肿瘤特征，生存率显著降低，且SB3-PD是死亡率的独立预测因子。HepG2/SB3PD细胞的侵袭能力明显高于HepG2/SB3WT。在THP-1细胞中，重组SB3-PD诱导的PDL1和IL-13水平高于SB3-WT。
SB3-PD异构体与肝癌患者较差的临床预后相关。这些发现在体外得到了细胞侵袭增加和损害免疫监视的分子产生增加的支持。
