Plasma long non-coding RNA, CoroMarker, a novel biomarker for diagnosis of coronary artery disease

Plasma long non-coding RNA, CoroMarker, a novel biomarker for diagnosis of coronary artery disease
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血浆长非编码 RNA,CoroMarker,一种用于诊断冠状动脉疾病的新型生物标志物。

DOI:
10.1042/cs20150121
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发表时间:
2015-10-01
期刊:
影响因子:
6
通讯作者:
Zeng, Chunyu
Zeng, Chunyu
中科院分区:
医学2区
文献类型:
--
作者:
Yang, Yujia;Cai, Yue;Zeng, Chunyu

文献摘要

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长链非编码RNA(lncRNA)已被报道参与心血管疾病(CVD)的发病机制,但循环lncRNA是否能作为冠状动脉疾病(CAD)的生物标志物尚不清楚。本研究通过微阵列分析从CAD患者和对照个体的血浆中筛选lncRNA,发现265个lncRNA差异表达。为了找到作为可能的CAD生物标志物候选物的特异性lncRNA,我们对174种上调的lncRNA使用以下标准:信号强度>= 8,倍数变化>2.5和P < 0.005。根据这些标准,鉴定了五种基因间lncRNA。通过定量PCR(qPCR)验证后,从候选列表中排除了一种lncRNA。其余四种lncRNA在另一个20名CAD患者和20名对照个体的人群中独立验证。受试者工作特征(ROC)曲线分析显示lncRNA AC 100865.1(简称CoroMarker)是这些lncRNA中最好的。血浆中CoroMarker水平也保持稳定。CoroMarker的预测价值在221名CAD患者和187名对照个体的更大队列中进一步评估。使用Fisher标准的诊断模型,考虑到风险因素,CoroMarker对CAD的最佳灵敏度从68.29%增加到78.05%,而特异性从91.89%略微下降到86.49%。CoroMarker在血浆中稳定,因为它主要存在于细胞外囊泡(EV)中,可能来自单核细胞。我们得出结论,CoroMarker是一种稳定、敏感和特异的CAD生物标志物。
Long non-coding RNAs (lncRNAs) have been reported to be involved in the pathogenesis of cardiovascular disease (CVD), but whether circulating lncRNAs can serve as a coronary artery disease (CAD), biomarker is not known. The present study screened lncRNAs by microarray analysis in the plasma from CAD patients and control individuals and found that 265 lncRNAs were differentially expressed. To find specific lncRNAs as possible CAD biomarker candidates, we used the following criteria for 174 up-regulated lncRNAs: signal intensity >= 8, fold change >2.5 and P < 0.005. According to these criteria, five intergenic lncRNAs were identified. After validation by quantitative PCR (qPCR), one lncRNA was excluded from the candidate list. The remaining four lncRNAs were independently validated in another population of 20 CAD patients and 20 control individuals. Receiver operating characteristic (ROC) curve analysis showed that lncRNA AC100865.1 (referred to as CoroMarker) was the best of these lncRNAs. CoroMarker levels were also stable in plasma. The predictive value of CoroMarker was further assessed in a larger cohort with 221 CAD patients and 187 control individuals. Using a diagnostic model with Fisher's criteria, taking the risk factors into account, the optimal sensitivity of CoroMarker for CAD increased from 68.29% to 78.05%, whereas the specificity decreased slightly from 91.89% to 86.49%. CoroMarker was stable in plasma because it was mainly in the extracellular vesicles (EVs), probably from monocytes. We conclude that CoroMarker is a stable, sensitive and specific biomarker for CAD.