TY - JOUR
T1 - Peripheral Blood MCEMP1 Gene Expression as a Biomarker for Stroke Prognosis
AU - Raman, Kripa
AU - O'Donnell, Martin J.
AU - Czlonkowska, Anna
AU - Duarte, Yan Carlos
AU - Lopez-Jaramillo, Patricio
AU - Penaherrera, Ernesto
AU - Sharma, Mike
AU - Shoamanesh, Ashkan
AU - Skowronska, Marta
AU - Yusuf, Salim
AU - Pare, Guillaume
N1 - Publisher Copyright:
© 2016 American Heart Association, Inc.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - 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.
AB - 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.
KW - Biomarkers
KW - blood
KW - gene expression profiling
KW - prognosis
KW - stroke
UR - http://www.scopus.com/inward/record.url?scp=84959545368&partnerID=8YFLogxK
U2 - 10.1161/STROKEAHA.115.011854
DO - 10.1161/STROKEAHA.115.011854
M3 - Artículo Científico
C2 - 26846866
AN - SCOPUS:84959545368
SN - 0039-2499
VL - 47
SP - 652
EP - 658
JO - Stroke
JF - Stroke
IS - 3
ER -