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

Author:

Marques Inês Soares12,Tavares Valéria134ORCID,Savva-Bordalo Joana5,Rei Mariana6,Liz-Pimenta Joana37ORCID,de Melo Inês Guerra13,Assis Joana8ORCID,Pereira Deolinda5,Medeiros Rui134910ORCID

Affiliation:

1. Molecular Oncology and Viral Pathology Group, Research Center 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

2. Faculty of Sciences of the University of Porto (FCUP), 4169-007 Porto, Portugal

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

4. Abel Salazar Institute for the Biomedical Sciences (ICBAS), University of Porto, 4050-313 Porto, Portugal

5. Department of Medical Oncology, Portuguese Institute of Oncology of Porto (IPO Porto), 4200-072 Porto, Portugal

6. Department of Gynaecology, Portuguese Institute of Oncology of Porto (IPO Porto), 4200-072 Porto, Portugal

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

8. Clinical Research Unit, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal

9. Faculty of Health Sciences, Fernando Pessoa University, 4200-150 Porto, Portugal

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

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.

Funder

IPO Porto

Fundação para a Ciência e Tecnologia

European Social Funds

national funds of MCTES

FCT/MCTES

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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