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卵巢肿瘤中的遗传变异性:一项基于医院的研究中对静脉血栓栓塞易感性和癌症预后的探索。

Heritable Genetic Variability in Ovarian Tumours: Exploring Venous Thromboembolism Susceptibility and Cancer Prognosis in a Hospital-Based Study.

作者信息

Tavares Valéria, Savva-Bordalo Joana, Rei Mariana, Liz-Pimenta Joana, Assis Joana, Pereira Deolinda, Medeiros Rui

机构信息

Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/Pathology and Laboratory Medicine Dep., Clinical Pathology SV/CI-IPOP @RISE(Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Centre (Porto. CCC), 4200-072 Porto, Portugal; ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal; Faculty of Medicine, University of Porto (FMUP), 4200-072 Porto, Portugal.

Department of Medical Oncology, Portuguese Institute of Oncology of Porto (IPO Porto), 4200-072 Porto, Portugal.

出版信息

Gene. 2025 May 20;950:149378. doi: 10.1016/j.gene.2025.149378. Epub 2025 Mar 1.

Abstract

Venous thromboembolism (VTE) is a frequently encountered paraneoplastic syndrome in patients with ovarian cancer (OC), an inflamm-aging entity. VTE is known to exacerbate their already poor prognosis, which is partially attributed to the contribution of the haemostatic system to ovarian tumourigenesis. In the past decade, numerous single-nucleotide polymorphisms (SNPs) implicated in VTE pathways have been proposed to influence tumour susceptibility and progression. These SNPs represent potential tools to improve the prognosis accuracy of OC patients. Hence, this study explored the influence of 12 haemostasis-associated SNPs on the risk for VTE, risk of OC progression and related death among 98 OC patients. The findings revealed a 20.5 % incidence of VTE, which was associated with more rapid disease progression and shorter survival times (log-rank test, p < 0.05). PROCR rs10747514 (AA/AG vs. GG; odds ratio (OR) = 3.67, p = 0.037) and SERPINE1 rs2070682 (CC/CT vs. TT; OR = 9.28, p = 0.040) were predictors of OC-related VTE development. Regarding patients' prognosis regardless of venous thrombogenesis, RGS7 rs2502448, F3 rs1361600, FGG rs2066865, and SERPINE1 rs2070682 were the most relevant biomarkers in different patient groups. These genetic variants might constitute attractive prognostic indicators among OC patients, offering insights to refine disease management strategies. However, due to the small cohort size and the study's retrospective nature, external validation is necessary to assess the generalisation of the findings.

摘要

静脉血栓栓塞症(VTE)是卵巢癌(OC)患者中常见的副肿瘤综合征,卵巢癌是一种与炎症衰老相关的疾病。已知VTE会加重卵巢癌患者本就不佳的预后,这部分归因于止血系统对卵巢肿瘤发生的作用。在过去十年中,许多与VTE通路相关的单核苷酸多态性(SNP)被认为会影响肿瘤易感性和进展。这些SNP是提高OC患者预后准确性的潜在工具。因此,本研究探讨了12个与止血相关的SNP对98例OC患者发生VTE的风险、OC进展风险及相关死亡的影响。研究结果显示,VTE的发生率为20.5%,这与疾病进展更快和生存时间更短相关(对数秩检验,p<0.05)。PROCR rs10747514(AA/AG与GG相比;比值比(OR)=3.67,p=0.037)和SERPINE1 rs2070682(CC/CT与TT相比;OR=9.28,p=0.040)是OC相关VTE发生的预测指标。对于不考虑静脉血栓形成的患者预后,RGS7 rs2502448、F3 rs1361600、FGG rs2066865和SERPINE1 rs2070682是不同患者组中最相关的生物标志物。这些基因变异可能是OC患者中有吸引力的预后指标,为优化疾病管理策略提供了思路。然而,由于队列规模较小且研究具有回顾性,需要外部验证来评估研究结果的普遍性。

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