학술논문

Discovery of novel plasma biomarkers for future incident venous thromboembolism by untargeted synchronous precursor selection mass spectrometry proteomics
Document Type
article
Source
Journal of Thrombosis and Haemostasis. 16(9)
Subject
Biomedical and Clinical Sciences
Cardiovascular Medicine and Haematology
Clinical Sciences
Prevention
Hematology
Biotechnology
4.1 Discovery and preclinical testing of markers and technologies
Detection
screening and diagnosis
Good Health and Well Being
Adult
Aged
Aged
80 and over
Biomarkers
Blood Proteins
Body Mass Index
Case-Control Studies
Female
Humans
Male
Middle Aged
Neoplasms
Prognosis
Prospective Studies
Proteomics
Pulmonary Embolism
Risk Assessment
Tandem Mass Spectrometry
Venous Thromboembolism
Venous Thrombosis
biomarkers
mass spectrometry
proteomics
venous thromboembolism
venous thrombosis
Cardiorespiratory Medicine and Haematology
Cardiovascular System & Hematology
Cardiovascular medicine and haematology
Clinical sciences
Language
Abstract
Essentials Discovery of predictive biomarkers of venous thromboembolism (VTE) may aid risk stratification. A case-control study where plasma was sampled before the occurrence of VTE was established. We generated untargeted plasma proteomic profiles of 200 individuals by use of mass spectrometry. Assessment of the biomarker potential of 501 proteins yielded 46 biomarker candidates.AbstractBackground Prophylactic anticoagulant treatment may substantially reduce the incidence of venous thromboembolism (VTE) but entails considerable risk of severe bleeding. Identification of individuals at high risk of VTE through the use of predictive biomarkers is desirable in order to achieve a favorable benefit-to-harm ratio. Objective We aimed to identify predictive protein biomarker candidates of VTE. Methods We performed a case-control study of 200 individuals that participated in the Tromsø Study, a population-based cohort, where blood samples were collected before the VTE events occurred. Untargeted tandem mass tag-synchronous precursor selection-mass spectrometry (TMT-SPS-MS3)-based proteomic profiling was used to study the plasma proteomes of each individual. Results Of the 501 proteins detected in a sufficient number of samples to allow multivariate analysis, 46 proteins were associated with VTE case-control status with P-values below the 0.05 significance threshold. The strongest predictive biomarker candidates, assessed by statistical significance, were transthyretin, vitamin K-dependent protein Z and protein/nucleic acid deglycase DJ-1. Conclusions Our untargeted approach of plasma proteome profiling revealed novel predictive biomarker candidates of VTE and confirmed previously reported candidates, thereby providing conceptual support for the validity of the study. A larger nested case-control study will be conducted to validate our findings.