Circulating microRNAs predict recurrence and death following venous thromboembolism

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Vincent Ten Cate - , Universitätsmedizin Mainz (Autor:in)
  • Steffen Rapp - , Universitätsmedizin Mainz (Autor:in)
  • Andreas Schulz - , Universitätsmedizin Mainz (Autor:in)
  • Alejandro Pallares Robles - , Universitätsmedizin Mainz (Autor:in)
  • Kerstin Jurk - , Universitätsmedizin Mainz (Autor:in)
  • Thomas Koeck - , Universitätsmedizin Mainz (Autor:in)
  • Christine Espinola-Klein - , Universitätsmedizin Mainz (Autor:in)
  • Michael Halank - , Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus Dresden (Autor:in)
  • Hans-Jürgen Seyfarth - , Universität Leipzig (Autor:in)
  • Manfred E Beutel - , Universitätsmedizin Mainz (Autor:in)
  • Alexander K Schuster - , Universitätsmedizin Mainz (Autor:in)
  • Federico Marini - , Universitätsmedizin Mainz (Autor:in)
  • Lukas Hobohm - , Universitätsmedizin Mainz (Autor:in)
  • Mareike Lankeit - , Charité – Universitätsmedizin Berlin (Autor:in)
  • Karl J Lackner - , Universitätsmedizin Mainz (Autor:in)
  • Wolfram Ruf - , Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK) - Partnerstandort Mainz, Scripps Research Institute, Universitätsmedizin Mainz (Autor:in)
  • Thomas Münzel - , Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK) - Partnerstandort Mainz, Universitätsmedizin Mainz (Autor:in)
  • Miguel A Andrade-Navarro - , Johannes Gutenberg-Universität Mainz (Autor:in)
  • Jürgen H Prochaska - , Universitätsmedizin Mainz (Autor:in)
  • Stavros V Konstantinides - , Charité – Universitätsmedizin Berlin (Autor:in)
  • Philipp S Wild - , Universitätsmedizin Mainz (Autor:in)

Abstract

BACKGROUND: Recurrent events frequently occur after venous thromboembolism (VTE) and remain difficult to predict based on established genetic, clinical, and proteomic contributors. The role of circulating microRNAs (miRNAs) has yet to be explored in detail.

OBJECTIVES: To identify circulating miRNAs predictive of recurrent VTE or death, and to interpret their mechanistic involvement.

METHODS: Data from 181 participants of a cohort study of acute VTE and 302 individuals with a history of VTE from a population-based cohort were investigated. Next-generation sequencing was performed on EDTA plasma samples to detect circulating miRNAs. The endpoint of interest was recurrent VTE or death. Penalized regression was applied to identify an outcome-relevant miRNA signature, and results were validated in the population-based cohort. The involvement of miRNAs in coregulatory networks was assessed using principal component analysis, and the associated clinical and molecular phenotypes were investigated. Mechanistic insights were obtained from target gene and pathway enrichment analyses.

RESULTS: A total of 1950 miRNAs were detected across cohorts after postprocessing. In the discovery cohort, 50 miRNAs were associated with recurrent VTE or death (cross-validated C-index, 0.65). A weighted miRNA score predicted outcome over an 8-year follow-up period (HRSD, 2.39; 95% CI, 1.98-2.88; P < .0001). The independent validation cohort validated 20 miRNAs (ORSD for score, 3.47; 95% CI, 2.37-5.07; P < .0001; cross-validated-area under the curve, 0.61). Principal component analysis revealed 5 miRNA networks with distinct relationships to clinical phenotype and outcome. Mapping of target genes indicated regulation via transcription factors and kinases involved in signaling pathways associated with fibrinolysis.

CONCLUSION: Circulating miRNAs predicted the risk of recurrence or death after VTE over several years, both in the acute and chronic phases.

Details

OriginalspracheEnglisch
Seiten (von - bis)2797-2810
Seitenumfang14
FachzeitschriftJournal of Thrombosis and Haemostasis
Jahrgang21
Ausgabenummer10
PublikationsstatusVeröffentlicht - Okt. 2023
Peer-Review-StatusJa

Externe IDs

Scopus 85169022527

Schlagworte

Schlagwörter

  • Humans, Circulating MicroRNA/genetics, Venous Thromboembolism/diagnosis, Cohort Studies, Proteomics, MicroRNAs/genetics