Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/Pathology and Laboratory Medicine Dep, Clinical Pathology SV/ RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto) / Porto Comprehensive Cancer Centre (Porto.CCC), Porto, 4200-072, Portugal.
Research Department, Portuguese League Against Cancer (NRNorte), Porto, 4200-172, Portugal.
J Thromb Thrombolysis. 2024 Jun;57(5):815-827. doi: 10.1007/s11239-024-02983-2. Epub 2024 Apr 20.
Venous thromboembolism (VTE) is a life-threatening haemostatic disease frequently diagnosed among the cancer population. The Khorana Score is currently the primal risk assessment model to stratify oncological patients according to their susceptibility to VTE, however, it displays a limited performance. Meanwhile, intensive research on VTE pathophysiology in the general population has uncovered a range of single-nucleotide polymorphisms (SNPs) associated with the condition. Nonetheless, their predictive ability concerning cancer-associated thrombosis (CAT) is controversial. Cervical cancer (CC) patients undergoing chemoradiotherapy often experience VTE, which negatively affects their survival. Thus, aiming for an improvement in thromboprophylaxis, new thrombotic biomarkers, including SNPs, are currently under investigation. In this study, the predictive capability of haemostatic gene SNPs on CC-related VTE and their prognostic value regardless of VTE were explored. Six SNPs in haemostatic genes were evaluated. A total of 401 CC patients undergoing chemoradiotherapy were enrolled in a retrospective cohort study. The implications for the time to VTE occurrence and overall survival (OS) were assessed. CAT considerably impacted the CC patients' OS (log-rank test, P < 0.001). SERPINE1 rs2070682 (T > C) showed a significant association with the risk of CC-related VTE (CC/CT vs. TT, log-rank test, P = 0.002; C allele, Cox model, hazard ratio (HR) = 6.99 and P = 0.009), while F2 rs1799963 (G > A) demonstrated an important prognostic value regardless of VTE (AA/AG vs. GG, log-rank test, P = 0.020; A allele, Cox model, HR = 2.76 and P = 0.026). For the remaining SNPs, no significant associations were detected. The polymorphisms SERPINE1 rs2070682 and F2 rs1799963 could be valuable tools in clinical decision-making, aiding in thromboprophylaxis and CC management, respectively.
静脉血栓栓塞症(VTE)是一种危及生命的止血性疾病,常在癌症患者中诊断。Khorana 评分目前是一种主要的风险评估模型,用于根据 VTE 的易感性对肿瘤患者进行分层,但是其性能有限。同时,对普通人群中 VTE 病理生理学的深入研究揭示了一系列与该疾病相关的单核苷酸多态性(SNP)。然而,它们对癌症相关血栓形成(CAT)的预测能力存在争议。接受放化疗的宫颈癌(CC)患者常发生 VTE,这会对其生存产生负面影响。因此,为了改善血栓预防,目前正在研究包括 SNP 在内的新血栓生物标志物。在这项研究中,我们探讨了止血基因 SNP 对 CC 相关 VTE 的预测能力及其无论是否发生 VTE 的预后价值。评估了止血基因中的 6 个 SNP。对接受放化疗的 401 例 CC 患者进行了回顾性队列研究。评估了对 VTE 发生时间和总生存期(OS)的影响。CAT 显著影响 CC 患者的 OS(对数秩检验,P<0.001)。SERPINE1 rs2070682(T>C)与 CC 相关 VTE 的风险显著相关(CC/CT 与 TT,对数秩检验,P=0.002;C 等位基因,Cox 模型,风险比(HR)=6.99,P=0.009),而 F2 rs1799963(G>A)无论是否发生 VTE均具有重要的预后价值(AA/AG 与 GG,对数秩检验,P=0.020;A 等位基因,Cox 模型,HR=2.76,P=0.026)。对于其余的 SNP,未发现显著相关性。SERPINE1 rs2070682 和 F2 rs1799963 多态性可能是临床决策中的有用工具,分别有助于血栓预防和 CC 管理。
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