title: Novel TIA biomarkers identified by mass spectrometry-based proteomics.
abstract: BACKGROUND
  Transient ischemic attacks remain a clinical diagnosis with significant variability between physicians. Finding reliable biomarkers to identify transient ischemic attacks would improve patient care and optimize treatment.
  
  
  OBJECTIVE
  Our aim is to identify novel serum TIA biomarkers through the use of mass spectroscopy-based proteomics.
  
  
  METHODS
  Patients with transient neurologic symptoms were prospectively enrolled. Mass spectrometry-based proteomics, an unbiased method to identify candidate proteins, was used to test the serum of the patients for biomarkers of cerebral ischemia. Three candidate proteins were found, and serum concentrations of these proteins were measured by enzyme-linked immunosorbent assay in a second cohort of prospectively enrolled patients. The Student's t-test was used for comparison. The Benjamini-Hochberg false discovery rate controlling procedure for multiple comparison adjustments determined significance for the proteomic screen.
  
  
  RESULTS
  Patients with transient ischemic attacks (n = 20), minor strokes (n = 15), and controls (i.e. migraine, seizure, n = 12) were enrolled in the first cohort. Ceruloplasmin, complement component C8 gamma (C8γ), and platelet basic protein were significantly different between the ischemic group (transient ischemic attack and minor stroke) and the controls (P = 0·0001, P = 0·00027, P = 0·00105, respectively). A second cohort of patients with transient ischemic attack (n = 22), minor stroke (n = 20), and controls' (n = 12) serum was enrolled. Platelet basic protein serum concentrations were increased in the ischemic samples compared with control (for transient ischemic attack alone, P = 0·019, for the ischemic group, P = 0·046). Ceruloplasmin trended towards increased concentrations in the ischemic group (P = 0·127); no significant difference in C8γ (P = 0·44) was found.
  
  
  CONCLUSIONS
  Utilizing mass spectrometry-based proteomics, platelet basic protein has been identified as a candidate serum biomarker for transient ischemic attack. This unbiased proteomic approach may be a promising method to identify novel biomarkers to more precisely diagnose transient ischemic attacks.
authors: Stanford Stroke Center, Department of Neurology, Stanford University, Stanford, CA, USA.|Department of Neurosurgery, Stanford University, Stanford, CA, USA.
authors: Paul M
authors: PM
authors: George
authors: Stanford Stroke Center, Department of Neurology, Stanford University, Stanford, CA, USA.
authors: Michael
authors: M
authors: Mlynash
authors: Stanford University Mass Spectrometry, Stanford University, Stanford, CA, USA.
authors: Christopher M
authors: CM
authors: Adams
authors: Department of Medicine, Stanford University, Stanford, CA, USA.
authors: Calvin J
authors: CJ
authors: Kuo
authors: Stanford Stroke Center, Department of Neurology, Stanford University, Stanford, CA, USA.
authors: Gregory W
authors: GW
authors: Albers
authors: Stroke Center, Department of Neurology, Hopital Pierre-Paul Riquet, Toulouse, France.
authors: Jean-Marc
authors: JM
authors: Olivot
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001774:Blood Chemical Analysis / Q000379:methods; D002570:Ceruloplasmin / Q000032:analysis; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D002546:Ischemic Attack, Transient / Q000097:blood*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D011446:Prospective Studies; D040901:Proteomics / Q000379:methods*; D012372:ROC Curve; D012680:Sensitivity and Specificity; D016037:Single-Blind Method; D020521:Stroke / Q000097:blood; D001620:beta-Thromboglobulin / Q000032:analysis*
chemical_list: D015415:Biomarkers; C061615:PPBP protein, human; D001620:beta-Thromboglobulin; D002570:Ceruloplasmin
keywords: biomarkers; ceruloplasmin; clinical trial; platelet basic protein; proteomics; transient ischemic attack