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. 2023 Dec 21;25(1):140.
doi: 10.3390/ijms25010140.

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

Inês Soares Marques  1   2 , Valéria Tavares  1   3   4 , Joana Savva-Bordalo  5 , Mariana Rei  6 , Joana Liz-Pimenta  3   7 , Inês Guerra de Melo  1   3 , Joana Assis  8 , Deolinda Pereira  5 , Rui Medeiros  1   3   4   9   10
Affiliations

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

Inês Soares Marques et al. Int J Mol Sci. .

Abstract

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.

Keywords: RNA; epithelial ovarian carcinoma; long non-coding; prognosis; thromboprophylaxis; venous thromboembolism.

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Conflict of interest statement

J.L.-P. has received a research Grant from GESCAT-Grupo de Estudos de Cancro e Trombose. This institution had no role in the decision to conduct the study, write and publish this manuscript. The remaining authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Progression-free survival (a) and overall survival (b) by Kaplan–Meier and log-rank test for ovarian cancer (OC) patients (n = 28), according to venous thromboembolism (VTE) occurrence after cancer diagnosis. (a) No association between VTE and patients’ progression-free survival (PFS) was observed among those with the condition after cancer diagnosis (log-rank test, p = 0.171). (b) Patients with VTE after OC diagnosis had lower overall survival (OS) compared to their counterparts (mean OS of 22.2 ± 5.6 months and 47.5 months ± 5.9 months, respectively; log-rank test, p = 0.028).
Figure 2
Figure 2
Normalised relative expression levels of lncRNAs (−∆Cq) in peripheral blood cells among ovarian cancer patients before and after the first-line chemotherapy: (a) MALAT1 expression; (b) TUG1 expression; (c) NEAT1 expression; (d) XIST expression; and (e) MEG8 expression; Wilcoxon matched-pairs signed rank test, * p < 0.05, ** p < 0.01; ns, non-significant.
Figure 3
Figure 3
Normalised relative expression levels of lncRNAs (−∆Cq) in peripheral blood cells among ovarian cancer patients in the context of venous thromboembolism (VTE): (a) MALAT1 expression; (b) TUG1 expression; (c) NEAT1 expression; (d) XIST expression; and (e) MEG8 expression; Mann–Whitney U test, * p < 0.05; ns, non-significant.
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