Discovery of prognostic biomarker candidates of lacunar infarction by quantitative proteomics of microvesicles enriched plasma

PLoS One. 2014 Apr 21;9(4):e94663. doi: 10.1371/journal.pone.0094663. eCollection 2014.

Abstract

Background: Lacunar infarction (LACI) is a subtype of acute ischemic stroke affecting around 25% of all ischemic stroke cases. Despite having an excellent recovery during acute phase, certain LACI patients have poor mid- to long-term prognosis due to the recurrence of vascular events or a decline in cognitive functions. Hence, blood-based biomarkers could be complementary prognostic and research tools.

Methods and finding: Plasma was collected from forty five patients following a non-disabling LACI along with seventeen matched control subjects. The LACI patients were monitored prospectively for up to five years for the occurrence of adverse outcomes and grouped accordingly (i.e., LACI-no adverse outcome, LACI-recurrent vascular event, and LACI-cognitive decline without any recurrence of vascular events). Microvesicles-enriched fractions isolated from the pooled plasma of four groups were profiled by an iTRAQ-guided discovery approach to quantify the differential proteome. The data have been deposited to the ProteomeXchange with identifier PXD000748. Bioinformatics analysis and data mining revealed up-regulation of brain-specific proteins including myelin basic protein, proteins of coagulation cascade (e.g., fibrinogen alpha chain, fibrinogen beta chain) and focal adhesion (e.g., integrin alpha-IIb, talin-1, and filamin-A) while albumin was down-regulated in both groups of patients with adverse outcome.

Conclusion: This data set may offer important insight into the mechanisms of poor prognosis and provide candidate prognostic biomarkers for validation on larger cohort of individual LACI patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood*
  • Blood Coagulation
  • Cell-Derived Microparticles / metabolism*
  • Chromatography
  • Cluster Analysis
  • Demography
  • Female
  • Focal Adhesions / metabolism
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Isotope Labeling
  • Middle Aged
  • Outcome Assessment, Health Care
  • Prognosis
  • Proteome / metabolism
  • Proteomics / methods*
  • Static Electricity
  • Stroke, Lacunar / blood*
  • Stroke, Lacunar / diagnosis*
  • Stroke, Lacunar / metabolism

Substances

  • Biomarkers
  • Proteome