title: Serum proteomics as a strategy to identify novel biomarkers of neurologic recovery after cardiac arrest: a feasibility study.
abstract: BACKGROUND
  Serum biomarkers may play a role in prognostication after cardiac arrest. This study was designed to assess the feasibility of using two-dimensional gel electrophoresis (2D-GE) coupled with mass spectrometry (MS) as a proteomic strategy to identify novel biomarkers that may predict neurological recovery.
  
  
  METHODS
  Adult comatose survivors of ventricular fibrillation or pulseless ventricular tachycardia were considered eligible. Blood was collected and serum separated within 6 h of hospital admission and then at 24 h afterwards. Neurological outcome was assessed at 3 months with the Cerebral Performance Category (CPC) score. Serum was assessed with 2D-GE with and without prior depletion of high abundance proteins. Protein differences between patients with good (CPC 1,2) vs. poor (CPC 3-5) neurological recovery were subsequently identified with MS.
  
  
  RESULTS
  From August 2010 to June 2014, 11 patients meeting eligibility criteria were recruited, from which serum was available from 9 (5 with good neurological outcome). On non-depleted serum, only high abundance acute phase proteins such as haptoglobin, cell-free hemoglobin, albumin, and amyloid were detected in both patients with good and poor neurological recovery. Following depletion of high abundance proteins, proteins identified by MS in both patient populations were the acute phase reactants c-reactive protein and retinol binding protein-4. Proteins uniquely identified in the serum of patients with poor neurological recovery included 14-3-3 (epsilon and zeta isoforms) and muskelin.
  
  
  CONCLUSIONS
  Two-D-GE coupled with MS is a feasible strategy to facilitate the identification of novel predictive biomarkers. The presence of muskelin and 14-3-3 in the serum of patients with poor neurological prognosis warrants further investigation.
authors.affiliation: Department of Critical Care Medicine, Queen's University/Kingston General Hospital, Kingston, Ontario, Canada. boydj@kgh.kari.net.|Queen's Centre for Neuroscience Studies, Queen's University, 2nd Floor, Botterell Hall, Kingston, Ontario, Canada. boydj@kgh.kari.net.|Department of Medicine (Neurology) and Critical Care, Davies 2, Kingston General Hospital, Kingston, ON, K7L 2V7, Canada. boydj@kgh.kari.net.
authors.forename: J Gordon
authors.initials: JG
authors.lastname: Boyd
authors.affiliation: Queen's Centre for Neuroscience Studies, Queen's University, 2nd Floor, Botterell Hall, Kingston, Ontario, Canada.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Smithson
authors.affiliation: Department of Critical Care Medicine, Queen's University/Kingston General Hospital, Kingston, Ontario, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Howes
authors.affiliation: Department of Critical Care Medicine, Queen's University/Kingston General Hospital, Kingston, Ontario, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Muscedere
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Kawaja
keywords: Biomarkers; Cardiac arrest; MALDI-TOF; Neuroprognostication; Prognosis; Serum proteomics; Targeted temperature management; Triple-quadropole mass spectrometry