Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing 210009, China.
Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China.
Clin Sci (Lond). 2018 Jul 31;132(14):1597-1614. doi: 10.1042/CS20180411.
Long noncoding RNAs (lncRNAs) have been highlighted to be involved in the pathological process of ischemic stroke (IS). The purpose of the present study was to investigate the expression profile of lncRNAs in peripheral blood mononuclear cells (PBMCs) of acute IS patients and to explore their utility as biomarkers of IS. Distinctive expression patterns of PBMC lncRNAs were identified by an lncRNA microarray and individual quantitative real-time PCR (qRT-PCR) in four independent sets for 206 IS, 179 healthy controls (HCs), and 55 patients with transient ischemic attack (TIA). A biomarker panel (lncRNA-based combination index) was established using logistic regression. LncRNA microarray analysis showed 70 up-regulated and 128 down-regulated lncRNAs in IS patients. Individual qRT-PCR validation demonstrated that three lncRNAs (linc-DHFRL1-4, SNHG15, and linc-FAM98A-3) were significantly up-regulated in IS patients compared with HCs and TIA patients. Longitudinal analysis of lncRNA expression up to 90 days after IS showed that linc-FAM98A-3 normalized to control levels by day 7, while SNHG15 remained increased, indicating the ability of lncRNAs to monitor IS dynamics. Receiver-operating characteristic (ROC) curve analysis showed that the lncRNA-based combination index outperformed serum brain-derived neurotrophic factor (BDNF) and neurone-specific enolase (NSE) in distinguishing IS patients from TIA patients and HCs with areas under ROC curve of more than 0.84. Furthermore, the combination index increased significantly after treatment and was correlated with neurological deficit severity of IS. The panel of these altered lncRNAs was associated with acute IS and could serve as a novel diagnostic method.
长链非编码 RNA（lncRNA）已被强调参与缺血性中风（IS）的病理过程。本研究的目的是研究急性 IS 患者外周血单个核细胞（PBMC）中 lncRNA 的表达谱，并探讨其作为 IS 生物标志物的用途。通过 lncRNA 微阵列和四个独立的 206 例 IS、179 例健康对照（HC）和 55 例短暂性脑缺血发作（TIA）患者的个体定量实时 PCR（qRT-PCR），确定了 PBMC lncRNA 的独特表达模式。使用逻辑回归建立了生物标志物谱（基于 lncRNA 的组合指数）。lncRNA 微阵列分析显示 IS 患者中有 70 个上调和 128 个下调的 lncRNA。个体 qRT-PCR 验证表明，与 HC 和 TIA 患者相比，IS 患者中有三个 lncRNA（linc-DHFRL1-4、SNHG15 和 linc-FAM98A-3）显著上调。IS 后长达 90 天的 lncRNA 表达的纵向分析表明，linc-FAM98A-3 在第 7 天恢复至对照水平，而 SNHG15 仍持续升高，表明 lncRNA 监测 IS 动态的能力。受试者工作特征（ROC）曲线分析表明，基于 lncRNA 的组合指数在区分 IS 患者与 TIA 患者和 HC 方面优于血清脑源性神经营养因子（BDNF）和神经元特异性烯醇化酶（NSE），ROC 曲线下面积超过 0.84。此外，该组合指数在治疗后显著增加，并且与 IS 神经功能缺损严重程度相关。这些改变的 lncRNA 与急性 IS 相关，可作为一种新的诊断方法。
