Gene expression profiling of blood for the prediction of ischemic stroke.
OBJECTIVE
A blood-based biomarker of acute ischemic stroke would be of significant value in clinical practice. This study aimed to (1) replicate in a larger cohort our previous study using gene expression profiling to predict ischemic stroke; and (2) refine prediction of ischemic stroke by including control groups relevant to ischemic stroke.


METHODS
Patients with ischemic stroke (n=70, 199 samples) were compared with control subjects who were healthy (n=38), had vascular risk factors (n=52), and who had myocardial infarction (n=17). Whole blood was drawn ≤3 hours, 5 hours, and 24 hours after stroke onset and from control subjects. RNA was processed on whole genome microarrays. Genes differentially expressed in ischemic stroke were identified and analyzed for predictive ability to discriminate stroke from control subjects.


RESULTS
The 29 probe sets previously reported predicted a new set of ischemic strokes with 93.5% sensitivity and 89.5% specificity. Sixty- and 46-probe sets differentiated control groups from 3-hour and 24-hour ischemic stroke samples, respectively. A 97-probe set correctly classified 86% of ischemic strokes (3 hour+24 hour), 84% of healthy subjects, 96% of vascular risk factor subjects, and 75% with myocardial infarction.


CONCLUSIONS
This study replicated our previously reported gene expression profile in a larger cohort and identified additional genes that discriminate ischemic stroke from relevant control groups. This multigene approach shows potential for a point-of-care test in acute ischemic stroke.
Stamova
Boryana
B
Department of Neurology and the MIND Institute, University of California at Davis, Sacramento, Calif 95817, USA. boryana.stamova@ucdmc.ucdavis.edu
Xu
Huichun
H
Jickling
Glen
G
Bushnell
Cheryl
C
Tian
Yingfang
Y
Ander
Bradley P
BP
Zhan
Xinhua
X
Liu
Dazhi
D
Turner
Renee
R
Adamczyk
Peter
P
Khoury
Jane C
JC
Pancioli
Arthur
A
Jauch
Edward
E
Broderick
Joseph P
JP
Sharp
Frank R
FR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002545:Brain Ischemia / Q000097:blood / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D012307:Risk Factors; D020521:Stroke / Q000097:blood / Q000235:genetics*
D015415:Biomarkers
Stroke. 2008 Oct;39(10):2902-9
18658039
Circulation. 2005 Jan 18;111(2):212-21
15630028
Expert Rev Cardiovasc Ther. 2009 Apr;7(4):389-93
19379063
Proc Natl Acad Sci U S A. 2002 May 14;99(10):6567-72
12011421
BMC Med Genomics. 2009 Aug 05;2:49
19656400
Circulation. 2006 Feb 14;113(6):e85-151
16407573
J Cereb Blood Flow Metab. 2006 Aug;26(8):1089-102
16395289
Bioinformatics. 2003 Jan 22;19(2):185-93
12538238
Stroke. 2008 Dec;39(12):3268-76
18772447
Neurology. 2009 Aug 4;73(5):393-9
19652144
Atherosclerosis. 2002 Mar;161(1):161-8
11882328