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

IF 5 2区医学 Q2 Medicine

Translational Oncology Pub Date : 2025-05-13 DOI:10.1016/j.tranon.2025.102413

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

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引用次数: 0

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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serpinB3-PD多态性对肝癌患者预后的影响

dhcc是癌症相关死亡的第三大原因，但目前的监测策略在早期阶段漏掉了超过三分之一的病例。丝氨酸蛋白酶抑制剂SerpinB3-PD （SB3-PD）是一种丝氨酸蛋白酶抑制剂的多态异构体，参与肿瘤发生和纤维发生，与更快的肝硬化失代偿有关。本研究探讨SB3-PD在HCC患者预后中的作用。方法对140例肝癌患者进行ssb3 - pd多态性分析，并对其进行随访。对过表达SB3野生型（HepG2/SB3WT）或PD亚型（HepG2/SB3PD）的HepG2细胞进行细胞侵袭分析。重组SB3-WT或SB3-PD对THP-1单核细胞系产生损害免疫监视分子的影响也被评估。结果携带SB3-PD多态性的患者表现出较差的肿瘤特征，与较低的生存率相关，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。结论sb3 - pd亚型与HCC患者临床预后不良相关。这些发现得到了体外细胞侵袭增加和免疫监视分子产生增加的支持。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Translational Oncology ONCOLOGY-

CiteScore

8.40

自引率

2.00%

发文量

314

审稿时长

54 days

期刊介绍： Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.