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Peripheral Blood MCEMP1 Gene Expression as a Biomarker for Stroke Prognosis
Kripa Raman1, Martin J O'Donnell1, Anna Czlonkowska1
1From 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.).
Background And Purpose:
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.
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