Proteome changes of plasma-derived extracellular vesicles in patients with myelodysplastic syndrome

PLoS One. 2022 Jan 10;17(1):e0262484. doi: 10.1371/journal.pone.0262484. eCollection 2022.

Abstract

Background: Extracellular vesicles are released into body fluids from the majority of, if not all, cell types. Because their secretion and specific cargo (e.g., proteins) varies according to pathology, extracellular vesicles may prove a rich source of biomarkers. However, their biological and pathophysiological functions are poorly understood in hematological malignancies.

Objective: Here, we investigated proteome changes in the exosome-rich fraction of the plasma of myelodysplastic syndrome patients and healthy donors.

Methods: Exosome-rich fraction of the plasma was isolated using ExoQuick™: proteomes were compared and statistically processed; proteins were identified by nanoLC-MS/MS and verified using the ExoCarta and QuickGO databases. Mann-Whitney and Spearman analyses were used to statistically analyze the data. 2D western blot was used to monitor clusterin proteoforms.

Results: Statistical analyses of the data highlighted clusterin alterations as the most significant. 2D western blot showed that the clusterin changes were caused by posttranslational modifications. Moreover, there was a notable increase in the clusterin proteoform in the exosome-rich fraction of plasma of patients with more severe myelodysplastic syndrome; this corresponded with a simultaneous decrease in their plasma.

Conclusions: This specific clusterin proteoform seems to be a promising biomarker for myelodysplastic syndrome progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood*
  • Case-Control Studies
  • Chromatography, Liquid
  • Extracellular Vesicles / metabolism*
  • Female
  • Humans
  • Male
  • Myelodysplastic Syndromes / metabolism
  • Myelodysplastic Syndromes / pathology*
  • Proteome / analysis
  • Proteome / metabolism*
  • Proteomics / methods*
  • Tandem Mass Spectrometry

Substances

  • Biomarkers
  • Proteome

Grants and funding

This work was supported by the Ministry of Health of the Czech Republic project for the conceptual development of the research organization (Institute of Hematology and Blood Transfusion, 00023736) - KP, PP, ZG, ZS, JC, PM. This work was supported by the Czech Science Foundation (grant number 20-10845S) - KP, PP, JC, PM. The funders played no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript for the infant’s postnatal assessment.