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CME Evaluation

Oral Communication Session

Venous Thromboembolism

Session: Cancer associated thrombosis - Mechanisms

OC 12.3 - MIR5683 predicts venous thromboembolism in advanced gastric cancer through regulation of thrombin generation, fibrinolysis and endothelial TFPI expression

Sunday, June 23, 2024
10:00 – 10:15 ICT
Room: Ballroom B2

    Presenting Author(s)

  • David Zaragoza Huesca, Degree in Biology and Master

    PhD student
    Department of Hematology and Medical Oncology, University General Hospital Morales Meseguer, Center of Hemodonation, University of Murcia, IMIB-Pascual Parrilla, 30003, Murcia, Spain
    Murcia, Murcia, Spain

    • Co-Author(s)

  • Julia Peñas Martínez, PhD Student

    PhD student
    Department of Hematology and Medical Oncology, University General Hospital Morales Meseguer, Center of Hemodonation, University of Murcia, IMIB-Pascual Parrilla, 30003, Murcia, Spain
    Murcia, Murcia, Spain

  • RT

    Raúl Teruel

    Doctor
    REGIONAL CENTER OF HEMODONATION, DEPARTMENT OF HEMATOLOGY AND MEDICAL ONCOLOGY, UNIVERSITY GENERAL HOSPITAL MORALES MESEGUER, UNIVERSITY OF MURCIA, IMIB-PASCUAL PARRILLA, 30003, MURCIA, SPAIN.
    Murcia, Murcia, Spain

  • GR

    Guillermo Ricote

    Doctor
    REGIONAL CENTER OF HEMODONATION, DEPARTMENT OF HEMATOLOGY AND MEDICAL ONCOLOGY, UNIVERSITY GENERAL HOSPITAL MORALES MESEGUER, UNIVERSITY OF MURCIA, IMIB-PASCUAL PARRILLA, 30003, MURCIA, SPAIN.
    Murcia, Murcia, Spain

  • AC

    Alberto Carmona Bayonas

    Doctor
    REGIONAL CENTER OF HEMODONATION, DEPARTMENT OF HEMATOLOGY AND MEDICAL ONCOLOGY, UNIVERSITY GENERAL HOSPITAL MORALES MESEGUER, UNIVERSITY OF MURCIA, IMIB-PASCUAL PARRILLA, 30003, MURCIA, SPAIN.
    Murcia, Murcia, Spain

  • AF

    Ana Fernández Montes

    Doctor
    Department of Medical Oncology, University-Hospital Complex of Ourense, 32005, Ourense, Spain
    Ourense, Galicia, Spain

  • PJ

    Paula Jiménez Fonseca

    Doctor
    Department of Medical Oncology, ISPA, Central University Hospital of Asturias, 33011, Oviedo, Spain
    Oviedo, Asturias, Spain

  • LM

    Lola Macia Rivas

    Doctor
    Department of Medical Oncology, ISPA, Central University Hospital of Asturias, 33011, Oviedo, Spain
    Oviedo, Asturias, Spain

  • PM

    Patricia Morales del burgo

    Doctor
    Department of Medical Oncology, ISPA, Central University Hospital of Asturias, 33011, Oviedo, Spain
    Oviedo, Asturias, Spain

  • LV

    Laura Visa

    Doctor
    Department of Medical Oncology, Hospital del Mar, 08003, Barcelona, Spain
    Barcelona, Catalonia, Spain

  • RH

    Raquel Hernández

    Doctor
    Department of Medical Oncology, University Hospital of Canarias, 38320, Santa Cruz de Tenerife, Spain
    Santa Cruz de Tenerife, Canarias, Spain

  • EM

    Eva Martínez de Castro

    Doctor
    Department of Medical Oncology, University Hospital Marqués de Valdecilla, 39008, Santander, Spain
    Santander, Cantabria, Spain

  • AP

    Andrea Pereira Elorrieta

    Doctor
    Department of Medical Oncology, University Hospital Marqués de Valdecilla, 39008, Santander, Spain
    Santander, Cantabria, Spain

  • María Eugenia de la Morena-Barrio, PhD

    PhD
    Servicio de Hematología, Hospital General Universitario Morales Messeguer, Centro Regional de Hemodonación, Universidad de Murcia, Universidad de Murcia, IMIB-Pascual Parrilla, CIBERER-ISCIII
    Murcia, Murcia, Spain

  • Pedro Garrido-Rodríguez

    PhD student
    Servicio de Hematología, Hospital General Universitario Morales Messeguer, Centro Regional de Hemodonación, Universidad de Murcia, Universidad de Murcia, IMIB-Pascual Parrilla, CIBERER-ISCIII
    Murcia, Murcia, Spain

  • ML

    María Luisa Lozano

    Hematologist
    Servicio de Hematología, Hospital General Universitario Morales Messeguer, Centro Regional de Hemodonación, Universidad de Murcia, Universidad de Murcia, IMIB-Pascual Parrilla, CIBERER-ISCIII
    Murcia, Murcia, Spain

  • Constantino Martínez

    Doctor
    Department of Hematology and Medical Oncology, University General Hospital Morales Meseguer, Center of Hemodonation, University of Murcia, IMIB-Pascual Parrilla, 30003, Murcia, Spain
    Murcia, Murcia, Spain

  • RG

    Rocío González-Conejero

    Doctor
    Department of Hematology and Medical Oncology, University General Hospital Morales Meseguer, Center of Hemodonation, University of Murcia, IMIB-Pascual Parrilla, 30003, Murcia, Spain
    Murcia, Murcia, Spain

  • Irene Martínez Martínez

    Researcher
    Servicio de Hematología, Hospital General Universitario Morales Messeguer, Centro Regional de Hemodonación, Universidad de Murcia, Universidad de Murcia, IMIB-Pascual Parrilla, CIBERER-ISCIII
    Murcia, Murcia, Spain

Background: Advanced gastric cancer (AGC) is one of the most thrombogenic neoplasms. Previously, we identified the microRNA MIR5683 overexpressed in AGC patients with venous thromboembolism (VTE) by transcriptomics (nested case-control [n=50vs50] study selected from the AGAMENON registry [n=4000]).

Aims: To validate MIR5683 as a VTE biomarker in a new cohort and to explore the underlying mechanisms.

Methods: RNA purification from AGC biopsies (n=44 VTE patients vs. 40 controls). RT-preamplification-digital PCR for absolute quantification of MIR5683 expression. Correlation with VTE occurrence by Mann-Whitney-test and ROC curve, and with VTE cumulative incidence by Cox-regression. Stable transfection of AGS and Kato-III cells with MIR5683/empty vector (AGS-MIR+/MIR-, Kato-III-MIR+/MIR-). Thrombin generation (TG) and fibrinolytic assays with platelet-poor plasma (PPP) previously incubated with cells. Quantitative proteomics of cell lines. Transient transfection of EA.hy926 cells with miR-5683 mimic and evaluation of TFPI (target according to TargetScanHuman) expression. Isolation of extracellular vesicles (EVs) from stably-transfected cells and incubation with EA.hy926.

Results: MIR5683 expression was significantly higher in VTE patients (p-value=0.025; ROC curve, AUC=0.625) (Figure-1A) and increased VTE risk with a significant hazard ratio (2.203, p-value=0.047) (Figure-1B). MIR5683 overexpression increased TG in PPP incubated with Kato-III and decreased fibrinolysis in PPP incubated with AGS and Kato-III (p-value < 0.05, Figure-2A). In AGS secretome, MIR5683 significantly downregulated MCP and SDC4, profibrinolytic proteins. In Kato-III lysate, MIR5683 significantly upregulated K2C1, a promoter of coagulation, and TSP1, a plasmin inhibitor (Figure-2B). In EA.hy926, miR-5683 transfection reduced secreted TFPI (p-value=0.026) (Figure-2C). MiR-5683 levels were higher in EA.hy926 incubated with EVs from AGS-MIR+ vs. EVs from AGS-MIR-, and increased miR-5683 levels reduced intracellular and secreted TFPI (Figure-2D & E).

Conclusion(s): MIR5683 was validated as a novel VTE biomarker in AGC patients. These findings could be based on anti-fibrinolyitic and pro-thrombotic effects of this miRNA, but also on its potential remote effect on endothelial TFPI.