Genomic biomarkers and cellular pathways of ischemic stroke by RNA gene expression profiling

Barr, Taura L.; Conley, Yvette P.; Ding, Jinhui; Dillman, Allissa; Warach, Steve; Singleton, Andrew; Matarı́n, Mar

doi:10.1212/wnl.0b013e3181f2b37f

Cited by 203 publications

(168 citation statements)

References 28 publications

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“…More recent RNA expression studies report similar findings to these first two studies. A study by Barr et al described a panel of 9 genes to distinguish stroke from controls [28]. Despite use of a different microarray platform (Illumina versus Affymetrix arrays), 5 of the 9 genes had been previous identified [27,28].…”

Section: Biomarkers For the Diagnosis Of Ischemic Strokementioning

confidence: 99%

Blood Biomarkers of Ischemic Stroke

2011

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This review provides a summary of the protein and RNA biomarkers that have been studied for the diagnosis and assessment of ischemic stroke. Many of the biomarkers identified relate to the pathophysiology of ischemic stroke, including ischemia of CNS tissue, acute thrombosis and inflammatory response. These biomarkers are summarized by their intended clinical application in ischemic stroke including diagnosis, prediction of stroke severity and outcome, and stratification of patients for stroke therapy. Among the biomarkers discussed are recent whole genome studies using RNA expression profiles to diagnose ischemic stroke and stroke etiology. Though many candidate blood based biomarkers for ischemic stroke have been identified, none are currently used in clinical practice. With further well designed study and careful validation, the development of blood biomarkers to improve the care of patients with ischemic stroke may be achieved.

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Section: Biomarkers For the Diagnosis Of Ischemic Strokementioning

confidence: 99%

Blood Biomarkers of Ischemic Stroke

2011

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“…In addition, expression was elevated in intracerebral hemorrhage when compared with ischemic stroke cases (P=3.9×10 development 7 ; therefore, peripheral blood RNA may be used in the clinic in the future. Both animal 8 and human 9,10 studies have observed unique RNA expression changes in whole blood after ischemic stroke. However, previous clinical studies were conducted on a relatively small sample size, consisting of a maximum of 39 ischemic stroke cases and 25 controls 9,10 and still require validation.…”

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confidence: 99%

“…Both animal 8 and human 9,10 studies have observed unique RNA expression changes in whole blood after ischemic stroke. However, previous clinical studies were conducted on a relatively small sample size, consisting of a maximum of 39 ischemic stroke cases and 25 controls 9,10 and still require validation. In addition, these studies have only assessed RNA biomarkers for stroke diagnosis, but not for stroke prognosis.…”

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confidence: 99%

Peripheral Blood MCEMP1 Gene Expression as a Biomarker for Stroke Prognosis

Raman

O’Donnell

Członkowska

et al. 2016

Stroke

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−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). 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. (Stroke. 2016;47:652-658.

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“…TTC7B and ischemic stroke risk T Krug et al studies have been performed on whole blood (Tang et al, 2006;Zhan et al, 2010;Barr et al, 2010) using PAXgene tubes and at times Nugen amplification methods. The use of PBMCs rather than whole blood has the advantage of increased detection sensitivity due to the very high levels of globin mRNA in erythrocytes, which represent B95% of all blood cells.…”

Section: Discussionmentioning

confidence: 99%

TTC7B Emerges as a Novel Risk Factor for Ischemic Stroke Through the Convergence of Several Genome-Wide Approaches

Krug

Gabriel²,

Taipa

et al. 2012

J Cereb Blood Flow Metab

100

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We hereby propose a novel approach to the identification of ischemic stroke (IS) susceptibility genes that involves converging data from several unbiased genetic and genomic tools. We tested the association between IS and genes differentially expressed between cases and controls, then determined which data mapped to previously reported linkage peaks and were nominally associated with stroke in published genome-wide association studies. We first performed gene expression profiling in peripheral blood mononuclear cells of 20 IS cases and 20 controls. Sixteen differentially expressed genes mapped to reported whole-genome linkage peaks, including the TTC7B gene, which has been associated with major cardiovascular disease. At the TTC7B locus, 46 tagging polymorphisms were tested for association in 565 Portuguese IS cases and 520 controls. Markers nominally associated in at least one test and defining associated haplotypes were then examined in 570 IS Spanish cases and 390 controls. Several polymorphisms and haplotypes in the intron 5-intron 6 region of TTC7B were also associated with IS risk in the Spanish and combined data sets. Multiple independent lines of evidence therefore support the role of TTC7B in stroke susceptibility, but further work is warranted to identify the exact risk variant and its pathogenic potential.

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Genomic biomarkers and cellular pathways of ischemic stroke by RNA gene expression profiling

Cited by 203 publications

References 28 publications

Blood Biomarkers of Ischemic Stroke

Blood Biomarkers of Ischemic Stroke

Peripheral Blood MCEMP1 Gene Expression as a Biomarker for Stroke Prognosis

TTC7B Emerges as a Novel Risk Factor for Ischemic Stroke Through the Convergence of Several Genome-Wide Approaches

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