Joana Liz-Pimenta

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

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, p = 0.013), while SELP upregulation was associated with shorter overall survival (log-rank test, p = 0.048). Dismissing patients with VTE before OC diagnosis, SELP rs6136 T allele carriers presented lower progression-free survival (log-rank test, p = 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.

Plasma microRNA Environment Linked to Tissue Factor Pathway and Cancer-Associated Thrombosis: Prognostic Significance in Ovarian Cancer

Ovarian cancer (OC) is a leading cause of death among gynaecological malignancies. The haemostatic system, which controls blood flow and prevents clotting disorders, paradoxically drives OC progression while increasing the risk of venous thromboembolism (VTE). MicroRNAs (miRNAs) have emerged as crucial in understanding VTE pathogenesis. Exploring the connection between cancer and thrombosis through these RNAs could lead to novel biomarkers of cancer-associated thrombosis (CAT) and OC, as well as potential therapeutic targets for tumour management. Thus, this study examined the impact of eight plasma miRNAs targeting the tissue factor (TF) coagulation pathway—miR-18a-5p, -19a-3p, -20a-5p, -23a-3p, -27a-3p, -103a-3p, -126-5p and -616-3p—in 55 OC patients. Briefly, VTE occurrence post-OC diagnosis was linked to shorter disease progression time (log-rank test, p = 0.024) and poorer overall survival (OS) (log-rank test, p < 0.001). High pre-chemotherapy levels of miR-20a-5p (targeting coagulation factor 3 (F3) and tissue factor pathway inhibitor 2 (TFPI2)) and miR-616-3p (targeting TFPI2) predicted VTE after OC diagnosis (χ2, p < 0.05). Regarding patients’ prognosis regardless of VTE, miR-20a-5p independently predicted OC progression (adjusted hazard ratio (aHR) = 6.13, p = 0.005), while miR-616-3p significantly impacted patients’ survival (aHR = 3.72, p = 0.020). Further investigation is warranted for their translation into clinical practice.

Long Non-Coding RNAs: Bridging Cancer-Associated Thrombosis and Clinical Outcome of Ovarian Cancer Patients

Ovarian cancer (OC) and venous thromboembolism (VTE) have a close relationship, in which tumour cells surpass the haemostatic system to drive cancer progression. Long non-coding RNAs (lncRNAs) have been implicated in VTE pathogenesis, yet their roles in cancer-associated thrombosis (CAT) and their prognostic value are unexplored. Understanding how these lncRNAs influence venous thrombogenesis and ovarian tumorigenesis may lead to the identification of valuable biomarkers for VTE and OC management. Thus, this study evaluated the impact of five lncRNAs, namely MALAT1, TUG1, NEAT1, XIST and MEG8, on a cohort of 40 OC patients. Patients who developed VTE after OC diagnosis had worse overall survival compared to their counterparts (log-rank test, p = 0.028). Elevated pre-chemotherapy MEG8 levels in peripheral blood cells (PBCs) predicted VTE after OC diagnosis (Mann–Whitney U test, p = 0.037; Χ2 test, p = 0.033). In opposition, its low levels were linked to a higher risk of OC progression (adjusted hazard ratio (aHR) = 3.00; p = 0.039). Furthermore, low pre-chemotherapy NEAT1 levels in PBCs were associated with a higher risk of death (aHR = 6.25; p = 0.008). As for the remaining lncRNAs, no significant association with VTE incidence, OC progression or related mortality was observed. Future investigation with external validation in larger cohorts is needed to dissect the implications of the evaluated lncRNAs in OC patients.