Endothelial Dysfunction Markers in Ovarian Cancer: Novel Study Connects the Markers to Thrombosis Risk and Tumour Prognosis

The poor prognosis of ovarian cancer, characterized by late diagnosis, high treatment resistance rates, and significant mortality, underscores the urgent need for improved prognostic and therapeutic strategies. In cancer patients, venous thromboembolism (VTE) is the second leading cause of death, with an even more pronounced impact in ovarian cancer due to the tumour’s biological characteristics, the surgical site, and the type of treatment. One of the key mechanisms underlying VTE is endothelial dysfunction (ED), a pro-inflammatory state of the endothelium that, independently of thrombosis, may also promote tumour progression.

A recent study conducted by the Molecular Oncology and Viral Pathology Group (GOMPV) at the Research Centre of IPO-Porto (CI-IPOP), in collaboration with Oncological Medicine Department, explored the relationship between endothelial dysfunction markers, VTE risk, and ovarian cancer prognosis. The researchers analysed the influence of genes encoding molecules involved in endothelial dysfunction, as well as single nucleotide polymorphisms (SNPs) within these genes, on the development of VTE and cancer progression, independently of tumour-associated thrombogenesis.

The results revealed that the overexpression of the NOS3(nitric oxide synthase 3) gene, responsible for the synthesis of nitric oxide - essential for endothelial health - was associated with a lower incidence of VTE, suggesting a potential protective role against thrombotic complications. Conversely, the overexpression of the SELP gene, which encodes P-selectin, was correlated with reduced overall survival, indicating that it may act as a negative prognostic factor in ovarian cancer. Furthermore, when excluding patients who developed VTE prior to cancer diagnosis, carriers of the T allele of SNP SELP rs6136 exhibited shorter progression-free survival. These findings suggest that endothelial dysfunction markers may have distinct roles in the clinical setting, influencing both tumour-associated thrombogenesis and cancer progression.

This research highlights the importance of vascular monitoring in ovarian cancer patients and opens new avenues for therapeutic approaches aimed at reducing the risk of thrombotic complications and improving disease prognosis.

Authors and Affiliations:

Inês Guerra de Melo ^1,2, Valéria Tavares ^1,2,3, Joana Savva-Bordalo ⁴, Mariana Rei ⁵, Joana Liz-Pimenta ^2,6, Deolinda Pereira ⁴ and Rui Medeiros ^1,2,3,7,8

¹ 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), 4200-072 Porto, Portugal;

² Faculty of Medicine, University of Porto (FMUP), 4200-072 Porto, Portugal;

³ ICBAS—Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal;

⁴ Department of Medical Oncology, Portuguese Institute of Oncology of Porto (IPO Porto), 4200-072 Porto, Portugal;

⁵ Department of Gynaecology, Portuguese Institute of Oncology of Porto (IPO Porto),
4200-072 Porto, Portugal;

⁶ Department of Medical Oncology, Centro Hospitalar de Trás-os-Montes e Alto Douro (CHTMAD), 5000-508 Vila Real, Portugal;

⁷ Faculty of Health Sciences, Fernando Pessoa University, 4200-150 Porto, Portugal;

⁸ Research Department, Portuguese League Against Cancer (NRNorte), 4200-172 Porto, Portugal.

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. NOS3 upregulation was linked to lower VTE incidence (χ²,  = 0.013), while SELP upregulation was associated with shorter overall survival (log-rank test,  = 0.048). Dismissing patients with VTE before OC diagnosis, SELP 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.

Journal: Life

Link: https://www.mdpi.com/2075-1729/14/12/1630