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    Oral Communication

    Venous Thromboembolism

    Molecular Insights in Cancer Associated Thrombosis

    OC 46.1 - Absolute quantitative proteomics for occult cancer screening in patient with unprovoked venous thromboembolism: results from the prospective PLATO-VTE study

    Monday, June 26, 2023
    14:45 – 15:00 ET
    Room: 510
    Session Available As: On-Demand

      Presenting Author(s)

    • NG

      Noori A.M Guman, MD

      PhD Student
      Dept. of Vascular Medicine, Amsterdam UMC location AMC, University of Amsterdam, Amsterdam, The Netherlands
      Amsterdam, Noord-Holland, Netherlands

      • Co-Author(s)

    • NK

      Noémie Kraaijpoel

      MD
      Department of Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
      Amsterdam, Noord-Holland, Netherlands

    • FM

      Frits I. Mulder

      PhD student
      Dept. of Vascular Medicine, Amsterdam UMC location AMC, University of Amsterdam, Amsterdam, The Netherlands
      Amsterdam, Noord-Holland, Netherlands

    • Marc Carrier, MD

      MD, MSc
      Ottawa Hospital Research Institute, Ottawa, ON, Canada
      Ottawa, Ontario, Canada

    • LJ

      Luis Jara-Palomares

      Senior consultant
      Hospital Universitario Virgen del Rocío, Seville, Spain
      Sevilla, Andalucia, Spain

    • MD

      Marcello Di Nisio

      MD
      Department of Medicine and Ageing Sciences, University G. D'Annunzio, Chieti, Italy
      Chieti, Abruzzi, Italy

    • Walter Ageno, MD (he/him/his)

      Professor of Medicine
      Department of Medicine and Surgery, University of Insubria, Varese, Italy
      Varese, Lombardia, Italy

    • Jan Beyer-Westendorf, MD,PhD

      Head of Division "Thrombosis and Hemostasis", Head of „Thrombosis Research“
      University Hospital “Carl Gustav Carus”, Technische Universität Dresden, Division of Hematology and Hemostasis, Department of Medicine I Thrombosis Research, Dresden, Saxony, Germany
      Dresden, Sachsen, Germany

    • Erik Klok, MD, PhD, FESC

      Leiden University Medical Center

    • Thomas Vanassche, MD PhD

      MD, PhD
      University Hospitals Leuven, Belgium
      Leuven, Vlaams-Brabant, Belgium

    • HO

      Hans-Martin M.B. Otten

      MD
      Dept. of Internal Medicine, Meander Medisch Centrum, Amersfoort, the Netherlands
      Amersfoort, Utrecht, Netherlands

    • BC

      Benilde Cosmi

      Associate Professor
      Dept. of Angiology and Blood Coagulation, S. Orsola-Malpighi University Hospital, IRCSS -University of Bologna, Bologna, Italy
      Bologna, Emilia-Romagna, Italy

    • PK

      Pieter W. Kamphuisen

      MD
      Tergooi MC and Amsterdam University Medical Centers
      Hilversum, Noord-Holland, Netherlands

    • VS

      Verónica Sánchez-López, PhD

      Postdoctoral Researcher
      Instituto de Biomedicina de Sevilla (IBiS). Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain.
      Seville, Andalucia, Spain

    • MB

      Myron G. Best

      MD
      Dept. of Neurosurgery, Brain Tumor Center Amsterdam, Cancer Center Amsterdam, Amsterdam UMC/Vrije Universiteit, Amsterdam, the Netherlands
      Amsterdam, Noord-Holland, Netherlands

    • PB

      Patrick M.M. Bossuyt

      Professor of Clinical Epidemiology
      Dept. of Epidemiology and Data Science, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
      Amsterdam, Noord-Holland, Netherlands

    • HV

      Henri Versteeg

      Professor
      Leiden University Medical Center
      Leiden, Zuid-Holland, Netherlands

    • Bv

      Bart J.M. van Vlijmen

      Associate professor
      Department of Internal Medicine, Division of Thrombosis and Hemostasis, Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands.
      Leiden, Zuid-Holland, Netherlands

    • Nick van Es, MD PhD (he/him/his)

      MD
      Department of Vascular Medicine, Amsterdam University Medical Center, Amsterdam, The Netherlands
      Amsterdam, Noord-Holland, Netherlands

    • Yassene Mohammed, PhD (he/him/his)

      Assistant professor
      Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands
      Leiden, Zuid-Holland, Netherlands

    Background: About 1 in 20 cases of unprovoked venous thromboembolism (VTE) have underlying cancer. Current guidelines suggest limited cancer screening, but 50% of cancers are not detected with this approach.

    Aims: The PLATO-VTE study is an international prospective cohort study evaluating novel biomarkers for occult cancer in patients with unprovoked VTE. Here we present results on biomarker candidates using absolute quantitative proteomics.

    Methods: Patients ≥40 years with a first unprovoked VTE and without a malignancy in the preceding 5 years were included after written informed consent was obtained. The primary outcome was an adjudicated cancer diagnosis during 12-month follow-up. We used quantitative mass spectrometry-based targeted proteomics with internal standards to measure concentrations of 269 coagulation, complement, and cancer pathway proteins, based on previously developed assays. Patients with cancer were compared to randomly selected unique controls (ratio 3:1) using a Student’s t-test. Discriminatory proteins with a P-value < 0.05 and fold change ≥15% in univariable analysis were combined in a logistic regression model. Accuracy was evaluated by the c-statistic, estimated by cross-validation with 100 iterations and 80/20% training/testing sets.

    Results: A total of 476 participants had completed 12-month follow-up, of whom 28 (5.9%) were diagnosed with cancer. Plasma samples were available for 24 (85.7%) cases for whom 78 control patients were randomly selected from the cohort (see Table for patient and cancer characteristics). Quantities of complement C7, β2-microglobulin, ICAM-1, lumican, and P-selectin were notably upregulated in cases compared with controls, whereas β-Ala-His dipeptidase, kalistatin, and coagulation factors VII and X were downregulated (Figure). The logistic regression model in which these nine proteins were combined had a c-statistic of 0.78 (95%-CI: 0.76-0.81).

    Conclusion(s): Plasma levels of nine circulating proteins were significantly different in patients with underlying cancer, suggesting potential of proteomics analysis as biomarker for occult cancer in patients with unprovoked VTE.

    Learning Objectives:

    • Recognize the need for occult cancer biomarkers for unprovoked venous thromboembolism patients.
    • Describe proteins significantly differentiated between unprovoked venous thromboembolism patients with and without a cancer diagnosis during 12 months follow-up.
    • Interpret the value of proteomics for occult cancer screening in patient with unprovoked venous thromboembolism.