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Elevated Expression of Two Circulating LncRNAs Predicts Poor Prognosis for Acute Cerebral Infarction

ABSTRACT: Poor prognosis for acute cerebral infarction (ACI) was suggested to be predicted using the high expression of some novel molecular markers, for example long non-coding RNAs (lncRNAs). Differentially expressed lncRNAs in peripheral whole blood from the ACI patients and healthy volunteers(HVT) were identified using microarray and further verified by qRT-PCR. The clinical outcome evaluated by 3-month modified Rankin Score (mRS), stroke stratification classified by OCSP criteria, and the expression characteristics of specific lncRNAs were analyzed in ACI patients. Among 5686 differentially expressed lncRNAs screened out by the microarray, nine were verified by qRT-PCR. Particularly, the expression of NR_120420 and lnc-GCH1-2:3 in the ACI group were significantly higher than the HVT group. ROC analysis showed that the sensitivity and specificity of NR_120420 were 85.7% and 84.6% in patients with total anterior circulation infarction (TACI) respectively(area under curve，AUC=0.861), while the sensitivity and specificity of lnc-GCH1-2:3 were 85.7% and 82.1% in patients with TACI respectively(AUC=0.802). Multivariate logistic regression showed that NR_120420 was a significantly independent diagnostic factor for ACI. The elevated expression levels of NR_120420 and lnc-GCH1-2:3 were associated with the TACI stroke classification and the poor prognosis of ACI. Our study clearly illustrated that the elevated expression levels of circulating NR_120420 and lnc-GCH1-2:3 could predict the TACI stroke classification with high sensitivity and specificity and the poor prognosis of patients with ACI.

ORGANISM(S): Homo sapiens

PROVIDER: GSE102541 | GEO | 2021/03/18

REPOSITORIES: GEO

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Project description:Indices for diagnosis of hyperacute cerebral infarction (HACI) and prediction of prognosis are essential for timely and appropriate management. MicroRNAs(miRNAs) regulating gene expression following stroke have potential use as prognostic markers of HACI. Here, we explored whether concentrations of circulating miRNAs could be correlated with clinical outcomes and thus form the basis of a system of stroke stratification. Plasma samples from patients with HACI (n = 7) and age-matched healthy volunteers (HVT, n = 4) were screened by microarray to find differentially expressed miRNAs, which were further verified by quantitative reverse transcription polymerase chain reaction(qRT-PCR) (HACI:HVT = 33:23). The target genes of the miRNAs with verified differential expression were investigated by GO and KEEG analysis. Using the TOAST (OCSP) criteria and the 3-month modified Rankin Score(mRS), relationships between the expression patterns of specific miRNAs, stroke stratification，and clinical prognosis were determined. The microarray analysis revealed 12 differentially expressed miRNAs. Among seven selected miRNAs verified with qRT-PCR, miR-16 expression in the HACI group was the most significantly different from the HVT group (P < 0.01). Bioinformatics analysis showed that the potential target genes of miR-16 were mainly involved in programmed cell death and the p53 signaling pathways. Receiver operating characteristic(ROC) analysis showed that the area under curve(AUC) of miR-16 was 0.775 (sensitivity 69.7% and specificity 87%) and 0.952 (sensitivity 100% and specificity 91.3%) in overall patients and patients with large artery atherosclerosis (LAAS), respectively. Elevated miR-16 expression was associated with the stroke subtype of LAAS, total anterior circulation infarction, partial anterior circulation infarction, and poor prognosis (P < 0.05). A diagnostic method based on rapid measurement of plasma miR-16 has potential to identify hyperacute cerebral infarction with LAAS with high sensitivity and specificity, which would inform and improve early treatment decisions and disease management.

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Elevated Expression of Two Circulating LncRNAs Predicts Poor Prognosis for Acute Cerebral Infarction

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