title: Peripheral Blood MCEMP1 Gene Expression as a Biomarker for Stroke Prognosis.
abstract: OBJECTIVE
  A limitation when making early decisions on stroke management is the lack of rapid diagnostic and prognostic testing. Our study sought to identify peripheral blood RNA biomarkers associated with stroke. The secondary aims were to assess the discriminative capacity of RNA biomarkers for primary stroke type and stroke prognosis at 1-month.
  
  
  METHODS
  Whole-blood gene expression profiling was conducted on the discovery cohort: 129 first-time stroke cases that had blood sampling within 5 days of symptom onset and 170 control participants with no history of stroke.
  
  
  RESULTS
  Through multiple regression analysis, we determined that expression of the gene MCEMP1 had the strongest association with stroke of 11 181 genes tested. MCEMP1 increased by 2.4-fold in stroke when compared with controls (95% confidence interval, 2.0-2.8; P=8.2×10(-22)). In addition, expression was elevated in intracerebral hemorrhage when compared with ischemic stroke cases (P=3.9×10(-4)). MCEMP1 was also highest soon after symptom onset and had no association with stroke risk factors. Furthermore, MCEMP1 expression independently improved discrimination of 1-month outcome. Indeed, discrimination models for disability and mortality that included MCEMP1 expression, baseline modified Rankin Scale score, and primary stroke type improved discrimination when compared with a model without MCEMP1 (disability Net Reclassification Index, 0.76; P=3.0×10(-6) and mortality Net Reclassification Index, 1.3; P=1.1×10(-9)). Significant associations with MCEMP1 were confirmed in an independent validation cohort of 28 stroke cases and 34 controls.
  
  
  CONCLUSIONS
  This study demonstrates that peripheral blood expression of MCEMP1 may have utility for stroke diagnosis and as a prognostic biomarker of stroke outcome at 1-month.
authors: From the Population Health Research Institute and Hamilton Health Sciences (K.R., M.O., M. Sharma, A.S., S.Y., G.P.), and Department of Medical Science (K.R.), Medicine (M.O.), Neurology (M. Sharma, A.S.), Clinical Epidemiology and Biostatistics (S.Y.), Pathology and Molecular Medicine (G.P.), McMaster University, Hamilton, Ontario, Canada; HRB-Clinical Research Facility, National University of Ireland, Galway, Ireland (M.O.); Second Department of Neurology, Institute of Psychiatry and Neurology, Warsaw Medical University, Warsaw, Poland (A.C., M. Skowronska); Luis Vernaza Hospital, Guayaquil, Ecuador (Y.C.D., E.P.); Ophthalmological Foundation of Santander, Floridablanca, Santander, Colombia (P.L.-J.); and Instituto MASIRA, School of Health Sciences, University of Santander (UDES), Bucaramanga, Santander, Colombia (P.L.-J.).
authors: Kripa
authors: K
authors: Raman
authors: From the Population Health Research Institute and Hamilton Health Sciences (K.R., M.O., M. Sharma, A.S., S.Y., G.P.), and Department of Medical Science (K.R.), Medicine (M.O.), Neurology (M. Sharma, A.S.), Clinical Epidemiology and Biostatistics (S.Y.), Pathology and Molecular Medicine (G.P.), McMaster University, Hamilton, Ontario, Canada; HRB-Clinical Research Facility, National University of Ireland, Galway, Ireland (M.O.); Second Department of Neurology, Institute of Psychiatry and Neurology, Warsaw Medical University, Warsaw, Poland (A.C., M. Skowronska); Luis Vernaza Hospital, Guayaquil, Ecuador (Y.C.D., E.P.); Ophthalmological Foundation of Santander, Floridablanca, Santander, Colombia (P.L.-J.); and Instituto MASIRA, School of Health Sciences, University of Santander (UDES), Bucaramanga, Santander, Colombia (P.L.-J.).
authors: Martin J
authors: MJ
authors: O'Donnell
authors: From the Population Health Research Institute and Hamilton Health Sciences (K.R., M.O., M. Sharma, A.S., S.Y., G.P.), and Department of Medical Science (K.R.), Medicine (M.O.), Neurology (M. Sharma, A.S.), Clinical Epidemiology and Biostatistics (S.Y.), Pathology and Molecular Medicine (G.P.), McMaster University, Hamilton, Ontario, Canada; HRB-Clinical Research Facility, National University of Ireland, Galway, Ireland (M.O.); Second Department of Neurology, Institute of Psychiatry and Neurology, Warsaw Medical University, Warsaw, Poland (A.C., M. Skowronska); Luis Vernaza Hospital, Guayaquil, Ecuador (Y.C.D., E.P.); Ophthalmological Foundation of Santander, Floridablanca, Santander, Colombia (P.L.-J.); and Instituto MASIRA, School of Health Sciences, University of Santander (UDES), Bucaramanga, Santander, Colombia (P.L.-J.).
authors: Anna
authors: A
authors: Czlonkowska
authors: From the Population Health Research Institute and Hamilton Health Sciences (K.R., M.O., M. Sharma, A.S., S.Y., G.P.), and Department of Medical Science (K.R.), Medicine (M.O.), Neurology (M. Sharma, A.S.), Clinical Epidemiology and Biostatistics (S.Y.), Pathology and Molecular Medicine (G.P.), McMaster University, Hamilton, Ontario, Canada; HRB-Clinical Research Facility, National University of Ireland, Galway, Ireland (M.O.); Second Department of Neurology, Institute of Psychiatry and Neurology, Warsaw Medical University, Warsaw, Poland (A.C., M. Skowronska); Luis Vernaza Hospital, Guayaquil, Ecuador (Y.C.D., E.P.); Ophthalmological Foundation of Santander, Floridablanca, Santander, Colombia (P.L.-J.); and Instituto MASIRA, School of Health Sciences, University of Santander (UDES), Bucaramanga, Santander, Colombia (P.L.-J.).
authors: Yan Carlos
authors: YC
authors: Duarte
authors: From the Population Health Research Institute and Hamilton Health Sciences (K.R., M.O., M. Sharma, A.S., S.Y., G.P.), and Department of Medical Science (K.R.), Medicine (M.O.), Neurology (M. Sharma, A.S.), Clinical Epidemiology and Biostatistics (S.Y.), Pathology and Molecular Medicine (G.P.), McMaster University, Hamilton, Ontario, Canada; HRB-Clinical Research Facility, National University of Ireland, Galway, Ireland (M.O.); Second Department of Neurology, Institute of Psychiatry and Neurology, Warsaw Medical University, Warsaw, Poland (A.C., M. Skowronska); Luis Vernaza Hospital, Guayaquil, Ecuador (Y.C.D., E.P.); Ophthalmological Foundation of Santander, Floridablanca, Santander, Colombia (P.L.-J.); and Instituto MASIRA, School of Health Sciences, University of Santander (UDES), Bucaramanga, Santander, Colombia (P.L.-J.).
authors: Patricio
authors: P
authors: Lopez-Jaramillo
authors: From the Population Health Research Institute and Hamilton Health Sciences (K.R., M.O., M. Sharma, A.S., S.Y., G.P.), and Department of Medical Science (K.R.), Medicine (M.O.), Neurology (M. Sharma, A.S.), Clinical Epidemiology and Biostatistics (S.Y.), Pathology and Molecular Medicine (G.P.), McMaster University, Hamilton, Ontario, Canada; HRB-Clinical Research Facility, National University of Ireland, Galway, Ireland (M.O.); Second Department of Neurology, Institute of Psychiatry and Neurology, Warsaw Medical University, Warsaw, Poland (A.C., M. Skowronska); Luis Vernaza Hospital, Guayaquil, Ecuador (Y.C.D., E.P.); Ophthalmological Foundation of Santander, Floridablanca, Santander, Colombia (P.L.-J.); and Instituto MASIRA, School of Health Sciences, University of Santander (UDES), Bucaramanga, Santander, Colombia (P.L.-J.).
authors: Ernesto
authors: E
authors: Peñaherrera
authors: From the Population Health Research Institute and Hamilton Health Sciences (K.R., M.O., M. Sharma, A.S., S.Y., G.P.), and Department of Medical Science (K.R.), Medicine (M.O.), Neurology (M. Sharma, A.S.), Clinical Epidemiology and Biostatistics (S.Y.), Pathology and Molecular Medicine (G.P.), McMaster University, Hamilton, Ontario, Canada; HRB-Clinical Research Facility, National University of Ireland, Galway, Ireland (M.O.); Second Department of Neurology, Institute of Psychiatry and Neurology, Warsaw Medical University, Warsaw, Poland (A.C., M. Skowronska); Luis Vernaza Hospital, Guayaquil, Ecuador (Y.C.D., E.P.); Ophthalmological Foundation of Santander, Floridablanca, Santander, Colombia (P.L.-J.); and Instituto MASIRA, School of Health Sciences, University of Santander (UDES), Bucaramanga, Santander, Colombia (P.L.-J.).
authors: Mike
authors: M
authors: Sharma
authors: From the Population Health Research Institute and Hamilton Health Sciences (K.R., M.O., M. Sharma, A.S., S.Y., G.P.), and Department of Medical Science (K.R.), Medicine (M.O.), Neurology (M. Sharma, A.S.), Clinical Epidemiology and Biostatistics (S.Y.), Pathology and Molecular Medicine (G.P.), McMaster University, Hamilton, Ontario, Canada; HRB-Clinical Research Facility, National University of Ireland, Galway, Ireland (M.O.); Second Department of Neurology, Institute of Psychiatry and Neurology, Warsaw Medical University, Warsaw, Poland (A.C., M. Skowronska); Luis Vernaza Hospital, Guayaquil, Ecuador (Y.C.D., E.P.); Ophthalmological Foundation of Santander, Floridablanca, Santander, Colombia (P.L.-J.); and Instituto MASIRA, School of Health Sciences, University of Santander (UDES), Bucaramanga, Santander, Colombia (P.L.-J.).
authors: Ashkan
authors: A
authors: Shoamanesh
authors: From the Population Health Research Institute and Hamilton Health Sciences (K.R., M.O., M. Sharma, A.S., S.Y., G.P.), and Department of Medical Science (K.R.), Medicine (M.O.), Neurology (M. Sharma, A.S.), Clinical Epidemiology and Biostatistics (S.Y.), Pathology and Molecular Medicine (G.P.), McMaster University, Hamilton, Ontario, Canada; HRB-Clinical Research Facility, National University of Ireland, Galway, Ireland (M.O.); Second Department of Neurology, Institute of Psychiatry and Neurology, Warsaw Medical University, Warsaw, Poland (A.C., M. Skowronska); Luis Vernaza Hospital, Guayaquil, Ecuador (Y.C.D., E.P.); Ophthalmological Foundation of Santander, Floridablanca, Santander, Colombia (P.L.-J.); and Instituto MASIRA, School of Health Sciences, University of Santander (UDES), Bucaramanga, Santander, Colombia (P.L.-J.).
authors: Marta
authors: M
authors: Skowronska
authors: From the Population Health Research Institute and Hamilton Health Sciences (K.R., M.O., M. Sharma, A.S., S.Y., G.P.), and Department of Medical Science (K.R.), Medicine (M.O.), Neurology (M. Sharma, A.S.), Clinical Epidemiology and Biostatistics (S.Y.), Pathology and Molecular Medicine (G.P.), McMaster University, Hamilton, Ontario, Canada; HRB-Clinical Research Facility, National University of Ireland, Galway, Ireland (M.O.); Second Department of Neurology, Institute of Psychiatry and Neurology, Warsaw Medical University, Warsaw, Poland (A.C., M. Skowronska); Luis Vernaza Hospital, Guayaquil, Ecuador (Y.C.D., E.P.); Ophthalmological Foundation of Santander, Floridablanca, Santander, Colombia (P.L.-J.); and Instituto MASIRA, School of Health Sciences, University of Santander (UDES), Bucaramanga, Santander, Colombia (P.L.-J.).
authors: Salim
authors: S
authors: Yusuf
authors: From the Population Health Research Institute and Hamilton Health Sciences (K.R., M.O., M. Sharma, A.S., S.Y., G.P.), and Department of Medical Science (K.R.), Medicine (M.O.), Neurology (M. Sharma, A.S.), Clinical Epidemiology and Biostatistics (S.Y.), Pathology and Molecular Medicine (G.P.), McMaster University, Hamilton, Ontario, Canada; HRB-Clinical Research Facility, National University of Ireland, Galway, Ireland (M.O.); Second Department of Neurology, Institute of Psychiatry and Neurology, Warsaw Medical University, Warsaw, Poland (A.C., M. Skowronska); Luis Vernaza Hospital, Guayaquil, Ecuador (Y.C.D., E.P.); Ophthalmological Foundation of Santander, Floridablanca, Santander, Colombia (P.L.-J.); and Instituto MASIRA, School of Health Sciences, University of Santander (UDES), Bucaramanga, Santander, Colombia (P.L.-J.). pareg@mcmasater.ca.
authors: Guillaume
authors: G
authors: Paré
mesh_terms: D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D038622:Internationality; D008297:Male; D008565:Membrane Proteins / Q000097:blood* / Q000235:genetics*; D011379:Prognosis; D020521:Stroke / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*
chemical_list: D015415:Biomarkers; C506757:MCEMP1 protein, human; D008565:Membrane Proteins
keywords: biomarkers; blood; gene expression profiling; prognosis; stroke