循环长链非编码RNA ENST00000507296是扩张型心肌病患者的一个预后指标。
Circulating Long Non-coding RNA ENST00000507296 Is a Prognostic Indicator in Patients with Dilated Cardiomyopathy.
作者信息
Zhang Xudong, Nie Xiang, Yuan Shuai, Li Huaping, Fan Jiahui, Li Chenze, Sun Yang, Zhao Yanru, Hou Huiying, Wang Dao Wen, Chen Chen
机构信息
Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiologic Disorders, Huazhong University of Science and Technology, Wuhan, China.
Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiologic Disorders, Huazhong University of Science and Technology, Wuhan, China.
出版信息
Mol Ther Nucleic Acids. 2019 Jun 7;16:82-90. doi: 10.1016/j.omtn.2019.02.004. Epub 2019 Feb 16.
BACKGROUND
Long non-coding RNAs (lncRNAs) participate in the pathogenesis of cardiovascular diseases. However, whether circulating lncRNAs serve as dilated cardiomyopathy (DCM) biomarkers remains unclear.
METHODS
Totally, 266 controls and 818 patients were enrolled. First, microarray-based circulating lncRNA profiling was performed in 10 normal controls and 10 patients with DCM. Second, the top 20 differentially expressed lncRNAs were validated by real-time qPCR in 64 controls and 64 DCM patients. Moreover, lncRNA sequencing was performed in three human heart-derived cell types, and the correlation between circulating lncRNA levels and the severity of heart failure was evaluated in the validated population. The validated two lncRNAs were assessed in 198 DCM patients and 198 matched controls. Finally, the sensitivity and specificity of circulating lncRNA expression in DCM diagnosis were evaluated using receiver-operating characteristic curve analysis, while Cox regression and Kaplan-Meier curve analysis were further performed in 552 DCM patients.
RESULTS
Eight candidate lncRNA biomarkers were obtained after microarray screening and real-time PCR validation. Among them, five were validated in the second cohort. However, only the levels of circulating lncRNA ENST00000507296 and ENST00000532365 were significantly correlated with the cardiac function, as well as detectable in at least one of the human heart-derived cell types by lncRNA-seq. Importantly, low circulating ENST00000507296 level was associated with high event-free survival in patients with DCM.
CONCLUSIONS
Circulating lncRNA ENST00000507296 was a prognostic biomarker in patients with DCM.
背景
长链非编码RNA（lncRNAs）参与心血管疾病的发病机制。然而，循环lncRNAs是否可作为扩张型心肌病（DCM）的生物标志物仍不清楚。
方法
共纳入266名对照者和818例患者。首先，对10名正常对照者和10例DCM患者进行基于微阵列的循环lncRNA谱分析。其次，通过实时定量PCR在64名对照者和64例DCM患者中验证前20个差异表达的lncRNAs。此外，对三种人心脏来源的细胞类型进行lncRNA测序，并在验证队列中评估循环lncRNA水平与心力衰竭严重程度之间的相关性。在198例DCM患者和198例匹配的对照者中评估验证的两种lncRNAs。最后，使用受试者工作特征曲线分析评估循环lncRNA表达在DCM诊断中的敏感性和特异性，同时对552例DCM患者进一步进行Cox回归和Kaplan-Meier曲线分析。
结果
经过微阵列筛选和实时PCR验证后获得了8种候选lncRNA生物标志物。其中，5种在第二个队列中得到验证。然而，只有循环lncRNA ENST00000507296和ENST00000532365的水平与心功能显著相关，并且通过lncRNA测序在至少一种人心脏来源的细胞类型中可检测到。重要的是，循环ENST00000507296水平低与DCM患者的高无事件生存率相关。
结论
循环lncRNA ENST00000507296是DCM患者的一种预后生物标志物。
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