Dataset Information

Obtaining Human Ischemic Stroke Gene Expression Biomarkers from Animal Models: A Cross-species Validation Study.

ABSTRACT: Recent studies have revealed the systematic altering of gene expression in human peripheral blood during the early stages of ischemic stroke, which suggests a new potential approach for the rapid diagnosis or prediction of stroke onset. Nevertheless, due to the difficulties of collecting human samples during proper disease stages, related studies are rather restricted. Many studies have instead been performed on manipulated animal models for investigating the regulation patterns of biomarkers during different stroke stages. An important inquiry is how well the findings of animal models can be replicated in human cases. Here, a method is proposed based on PageRank scores of miRNA-mRNA interaction network to select ischemic stroke biomarkers derived from rat brain samples, and biomarkers are validated with two human peripheral blood gene expression datasets. Hierarchical clustering results revealed that the achieved biomarkers clearly separate the blood gene expression of stroke patients and healthy people. Literature searches and functional analyses further validated the biological significance of these biomarkers. Compared to the traditional methods, such as differential expression, the proposed approach is more stable and accurate in detecting cross-species biomarkers with biological relevance, thereby suggesting an efficient approach of re-using gene biomarkers obtained from animal-model studies for human diseases.

SUBMITTER: Wang Y

PROVIDER: S-EPMC4942769 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Obtaining Human Ischemic Stroke Gene Expression Biomarkers from Animal Models: A Cross-species Validation Study.

Wang Yingying Y Cai Yunpeng Y

Scientific reports 20160713

Recent studies have revealed the systematic altering of gene expression in human peripheral blood during the early stages of ischemic stroke, which suggests a new potential approach for the rapid diagnosis or prediction of stroke onset. Nevertheless, due to the difficulties of collecting human samples during proper disease stages, related studies are rather restricted. Many studies have instead been performed on manipulated animal models for investigating the regulation patterns of biomarkers du ...[more]

PMID: 27407070

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Project description:Stroke is the world's second leading cause of mortality, with a high incidence of severe morbidity in surviving victims. There are currently relatively few treatment options available to minimize tissue death following a stroke. As such, there is a pressing need to explore, at a molecular, cellular, tissue, and whole body level, the mechanisms leading to damage and death of CNS tissue following an ischemic brain event. This review explores the etiology and pathogenesis of ischemic stroke, and provides a general model of such. The pathophysiology of cerebral ischemic injury is explained, and experimental animal models of global and focal ischemic stroke, and in vitro cellular stroke models, are described in detail along with experimental strategies to analyze the injuries. In particular, the technical aspects of these stroke models are assessed and critically evaluated, along with detailed descriptions of the current best-practice murine models of ischemic stroke. Finally, we review preclinical studies using different strategies in experimental models, followed by an evaluation of results of recent, and failed attempts of neuroprotection in human clinical trials. We also explore new and emerging approaches for the prevention and treatment of stroke. In this regard, we note that single-target drug therapies for stroke therapy, have thus far universally failed in clinical trials. The need to investigate new targets for stroke treatments, which have pleiotropic therapeutic effects in the brain, is explored as an alternate strategy, and some such possible targets are elaborated. Developing therapeutic treatments for ischemic stroke is an intrinsically difficult endeavour. The heterogeneity of the causes, the anatomical complexity of the brain, and the practicalities of the victim receiving both timely and effective treatment, conspire against developing effective drug therapies. This should in no way be a disincentive to research, but instead, a clarion call to intensify efforts to ameliorate suffering and death from this common health catastrophe. This review aims to summarize both the present experimental and clinical state-of-the art, and to guide future research directions.

Project description:Background and purposePrediction models for outcome of patients with acute ischemic stroke who will undergo endovascular treatment have been developed to improve patient management. The aim of the current study is to provide an overview of preintervention models for functional outcome after endovascular treatment and to validate these models with data from daily clinical practice.MethodsWe systematically searched within Medline, Embase, Cochrane, Web of Science, to include prediction models. Models identified from the search were validated in the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) registry, which includes all patients treated with endovascular treatment within 6.5 hours after stroke onset in the Netherlands between March 2014 and November 2017. Predictive performance was evaluated according to discrimination (area under the curve) and calibration (slope and intercept of the calibration curve). Good functional outcome was defined as a score of 0-2 or 0-3 on the modified Rankin Scale depending on the model.ResultsAfter screening 3468 publications, 19 models were included in this validation. Variables included in the models mainly addressed clinical and imaging characteristics at baseline. In the validation cohort of 3156 patients, discriminative performance ranged from 0.61 (SPAN-100 [Stroke Prognostication Using Age and NIH Stroke Scale]) to 0.80 (MR PREDICTS). Best-calibrated models were THRIVE (The Totaled Health Risks in Vascular Events; intercept -0.06 [95% CI, -0.14 to 0.02]; slope 0.84 [95% CI, 0.75-0.95]), THRIVE-c (intercept 0.08 [95% CI, -0.02 to 0.17]; slope 0.71 [95% CI, 0.65-0.77]), Stroke Checkerboard score (intercept -0.05 [95% CI, -0.13 to 0.03]; slope 0.97 [95% CI, 0.88-1.08]), and MR PREDICTS (intercept 0.43 [95% CI, 0.33-0.52]; slope 0.93 [95% CI, 0.85-1.01]).ConclusionsThe THRIVE-c score and MR PREDICTS both showed a good combination of discrimination and calibration and were, therefore, superior in predicting functional outcome for patients with ischemic stroke after endovascular treatment within 6.5 hours. Since models used different predictors and several models had relatively good predictive performance, the decision on which model to use in practice may also depend on simplicity of the model, data availability, and the comparability of the population and setting.

Dataset Information

Obtaining Human Ischemic Stroke Gene Expression Biomarkers from Animal Models: A Cross-species Validation Study.

Publications

Obtaining Human Ischemic Stroke Gene Expression Biomarkers from Animal Models: A Cross-species Validation Study.

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