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卵巢癌中的内皮功能障碍标志物:静脉血栓栓塞风险与肿瘤预后结果

Endothelial Dysfunction Markers in Ovarian Cancer: VTE Risk and Tumour Prognostic Outcomes.

作者信息

de Melo Inês Guerra, Tavares Valéria, Savva-Bordalo Joana, Rei Mariana, Liz-Pimenta Joana, Pereira Deolinda, Medeiros Rui

机构信息

Molecular Oncology and Viral Pathology Group, Research Centre of IPO Porto (CI-IPOP), Pathology and Laboratory Medicine Department, Clinical Pathology SV/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Centre (Porto. CCC), 4200-072 Porto, Portugal.

Faculty of Medicine, University of Porto (FMUP), 4200-072 Porto, Portugal.

出版信息

Life (Basel). 2024 Dec 9;14(12):1630. doi: 10.3390/life14121630.

Abstract

Ovarian cancer (OC) presents daunting lethality rates worldwide, with frequent late-stage diagnosis and chemoresistance, highlighting the need for improved prognostic approaches. Venous thromboembolism (VTE), a major cancer mortality factor, is partially driven by endothelial dysfunction (ED). ED's pro-inflammatory state fosters tumour progression, suggesting a VTE-independent link between ED and cancer. Given this triad's interplay, ED markers may influence OC behaviour and patients' prognosis. Thus, the impact of ED-related genes and single-nucleotide polymorphisms (SNPs) on OC-related VTE and patient thrombogenesis-independent prognosis was investigated. upregulation was linked to lower VTE incidence (χ, = 0.013), while upregulation was associated with shorter overall survival (log-rank test, = 0.048). Dismissing patients with VTE before OC diagnosis, rs6136 T allele carriers presented lower progression-free survival (log-rank test, = 0.038). Nevertheless, due to the SNP minor allele underrepresentation, further investigation is required. Taken together, ED markers seem to exhibit roles that depend on the clinical context, such as tumour-related thrombogenesis or cancer prognosis. Validation with larger cohorts and more in-depth functional studies are needed for data clarification and potential therapeutic strategies exploitation to tackle cancer progression and thrombosis in OC patients.

摘要

卵巢癌(OC)在全球范围内呈现出令人畏惧的致死率,其诊断往往处于晚期且具有化疗耐药性,这凸显了改进预后方法的必要性。静脉血栓栓塞(VTE)是癌症死亡的一个主要因素,部分是由内皮功能障碍(ED)驱动的。ED的促炎状态促进肿瘤进展,这表明ED与癌症之间存在不依赖于VTE的联系。考虑到这三者之间的相互作用,ED标志物可能会影响OC的行为和患者的预后。因此,研究了与ED相关的基因和单核苷酸多态性(SNP)对OC相关VTE和患者不依赖血栓形成的预后的影响。上调与较低的VTE发生率相关(χ²,P = 0.013),而上调与较短的总生存期相关(对数秩检验,P = 0.048)。在OC诊断前排除患有VTE的患者,rs6136 T等位基因携带者的无进展生存期较低(对数秩检验,P = 0.038)。然而,由于SNP次要等位基因的代表性不足,需要进一步研究。综上所述,ED标志物似乎表现出依赖于临床背景的作用,如肿瘤相关的血栓形成或癌症预后。需要用更大的队列进行验证并开展更深入的功能研究,以澄清数据并开发潜在的治疗策略,从而应对OC患者的癌症进展和血栓形成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ce0/11678387/6f9daec2be46/life-14-01630-g001.jpg

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