Dataset Information

Altered expression of long noncoding RNAs in peripheral blood mononuclear cells in patients with impaired leptomeningeal collaterals after acute anterior large vessel occlusions.

ABSTRACT: Background:In the event of acute ischemic stroke (AIS) due to anterior large vessel occlusion (aLVO), leptomeningeal collaterals (LMCs) status is a key factor to define the severity and functional prognosis of this disease. However, the extent of LMCs exhibits substantial variability among the patients, which is genetic determined. Long non-coding RNAs (lncRNAs) expression profiles in human peripheral blood have been found to be altered after AIS. But whether there are specific lncRNAs correlated with LMC status in aLVO has not yet been investigated. Methods:Differential lncRNA expression panels in peripheral blood mononuclear cells (PBMCs) were assessed by microarray analysis and individual quantitative real-time polymerase chain reaction (RT-PCR) in three independent sets consist of 134 patients with aLVO and 73 healthy controls (HCs). LMCs Status in those patients was assessed based on baseline computed tomographic angiography (CTA). Results:Microarray analysis showed 23 differentially expressed lncRNAs in patients with poor LMCs status. After independent validations by RT-PCR, lncRNA ENST00000422956 was found to be significantly downregulated in patients with poor LMCs status. Receiver-operating characteristic (ROC) analysis revealed the area under the ROC curve (AUC) for ENST00000422956 to predict poor LMCs status was 0.749. Moreover, ENST00000422956 expression level and baseline National Institutes of Health Stroke Scale (NIHSS) score were identified as independent predictors for impaired LMCs, and a significantly positive correlation was observed between ENST00000422956 expression level and LMCs status. Via cis-regulatory analysis, paired box 8 (Pax8) was identified as the target gene for ENST00000422956. Conclusions:The dysregulated lncRNA ENST00000422956 in PBMCs was associated with impairment of LMCs in patients with aLVO, suggesting that measurement of circulatory lncRNAs might be included as possible biomarkers for evaluation of LMCs status in AIS. More importantly, this might be the foundation for understand the potential roles of lncRNAs in LMCs formation after ischemic stroke.

SUBMITTER: Wu Q

PROVIDER: S-EPMC6861772 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Altered expression of long noncoding RNAs in peripheral blood mononuclear cells in patients with impaired leptomeningeal collaterals after acute anterior large vessel occlusions.

Wu Qisi Q Li Ting T Zhu Dan D Lv Fajin F Qin Xinyue X

Annals of translational medicine 20191001 20

<h4>Background</h4>In the event of acute ischemic stroke (AIS) due to anterior large vessel occlusion (aLVO), leptomeningeal collaterals (LMCs) status is a key factor to define the severity and functional prognosis of this disease. However, the extent of LMCs exhibits substantial variability among the patients, which is genetic determined. Long non-coding RNAs (lncRNAs) expression profiles in human peripheral blood have been found to be altered after AIS. But whether there are specific lncRNAs c ...[more]

PMID: 31807505

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Project description:Diffusion-weighted imaging (DWI) Alberta Stroke Program Early CT Score (ASPECTS), a surrogate of infarct volume, predicts outcome in anterior large vessel occlusion strokes. We aim to determine whether topological information captured by DWI ASPECTS contributes additional prognostic value.Adults with intracranial internal carotid artery, M1 or M2 middle carotid artery occlusions who underwent endovascular therapy were included. The primary outcome measure was poor clinical outcome (3-month modified Rankin Scale score, 3-6). Prognostic value of the 10 DWI ASPECTS regions in predicting poor outcome was determined by multivariable logistic regression, controlling for final infarct volume, age, and laterality.Two hundred and thirteen patients (mean age, 66.1±14.5 years; median National Institutes of Health Stroke Scale, 15) were included. Inter-rater reliability was good for DWI ASPECTS (deep regions, ?=0.72; cortical regions, ?=0.63). All DWI ASPECTS regions with the exception of the putamen were significant predictors (P<0.05) of poor outcome in univariate analyses. Statistical collinearity among ASPECTS regions was not observed. Using penalized multivariable logistic regression, only M4 (odds ratio, 2.82; 95% confidence interval, 1.39-5.76) and M6 (odds ratio, 2.45; 95% confidence interval, 1.15-5.3) involvement were associated with poor outcome. M6 involvement independently predicted poor outcome in right hemispheric strokes (odds ratio, 5.8; 95% confidence interval, 1.9-20.3), whereas M4 (odds ratio, 4.3; 95% confidence interval, 1.3-15.0) involvement predicted poor outcome in left hemispheric strokes adjusting for infarct volume. Topologic information modestly improved the predictive ability of a prognostic score that incorporates age, infarct volume, and hemorrhagic transformation.Involvement of the right parieto-occipital (M6) and left superior frontal (M4) regions affect clinical outcome in anterior large vessel occlusions over and above the effect of infarct volume and should be considered during prognostication.

Project description:Background and Purpose- Accurate and rapid detection of anterior circulation large vessel occlusion (LVO) is of paramount importance in patients with acute stroke due to the potentially rapid infarction of at-risk tissue and the limited therapeutic window for endovascular clot retrieval. Hence, the optimal threshold of a new, fully automated software-based approach for LVO detection was determined, and its diagnostic performance evaluated in a large cohort study. Methods- For this retrospective study, data were pooled from: 2 stroke trials, DEFUSE 2 (n=62; 07/08-09/11) and DEFUSE 3 (n=213; 05/17-05/18); a cohort of endovascular clot retrieval candidates (n=82; August 2, 2014-August 30, 2015) and normals (n=111; June 6, 2017-January 28, 2019) from a single quaternary center; and code stroke patients (n=501; January 1, 2017-December 31, 2018) from a single regional hospital. All CTAs were assessed by the automated algorithm. Consensus reads by 2 neuroradiologists served as the reference standard. ROC analysis was used to assess diagnostic performance of the algorithm for detection of (1) anterior circulation LVOs involving the intracranial internal carotid artery or M1 segment middle cerebral artery (M1-MCA); (2) anterior circulation LVOs and proximal M2 segment MCA (M2-MCA) occlusions; and (3) individual segment occlusions. Results- CTAs from 926 patients (median age 70 years, interquartile range: 58-80; 422 females) were analyzed. Three hundred ninety-five patients had an anterior circulation LVO or M2-MCA occlusion (National Institutes of Health Stroke Scale 14 [median], interquartile range: 9-19). Sensitivity and specificity were 97% and 74%, respectively, for LVO detection, and 95% and 79%, respectively, when M2 occlusions were included. On analysis by occlusion site, sensitivities were 90% (M2-MCA), 97% (M1-MCA), and 97% (intracranial internal carotid artery) with corresponding area-under-the-ROC-curves of 0.874 (M2), 0.962 (M1), and 0.997 (intracranial internal carotid artery). Conclusions- Intracranial anterior circulation LVOs and proximal M2 occlusions can be rapidly and reliably detected by an automated detection tool, which may facilitate intra- and inter-instutional workflows and emergent imaging triage in the care of patients with stroke.

Dataset Information

Altered expression of long noncoding RNAs in peripheral blood mononuclear cells in patients with impaired leptomeningeal collaterals after acute anterior large vessel occlusions.

Publications

Altered expression of long noncoding RNAs in peripheral blood mononuclear cells in patients with impaired leptomeningeal collaterals after acute anterior large vessel occlusions.

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