Department of Cardiology, Daping Hospital, Third Military Medical University, Chongqing, China Chongqing Institute of Cardiology, Chongqing, China.
Department of Cardiology, Daping Hospital, Third Military Medical University, Chongqing, China Department of Physiology and Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA, U.S.A.
Clin Sci (Lond). 2015 Oct 1;129(8):675-85. doi: 10.1042/CS20150121. Epub 2015 Jun 11.
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.
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 是否可以作为冠心病（CAD）的生物标志物尚不清楚。本研究通过对 CAD 患者和对照个体血浆中的 lncRNA 进行微阵列分析，筛选出 265 个差异表达的 lncRNA。为了找到作为可能的 CAD 生物标志物候选物的特异性 lncRNA，我们使用以下标准对 174 个上调的 lncRNA 进行了筛选：信号强度≥8，倍数变化>2.5，P<0.005。根据这些标准，鉴定出 5 个基因间 lncRNA。通过定量 PCR（qPCR）验证后，一个 lncRNA 被排除在候选名单之外。其余 4 个 lncRNA 在另一个 20 例 CAD 患者和 20 例对照个体的人群中进行了独立验证。受试者工作特征（ROC）曲线分析显示，lncRNA AC100865.1（称为 CoroMarker）是这些 lncRNA 中最好的一个。CoroMarker 水平在血浆中也很稳定。在一个包含 221 例 CAD 患者和 187 例对照个体的更大队列中，进一步评估了 CoroMarker 的预测值。使用 Fisher 标准的诊断模型，考虑到危险因素，CoroMarker 对 CAD 的最佳敏感性从 68.29%增加到 78.05%，而特异性则从 91.89%略有下降至 86.49%。CoroMarker 在血浆中稳定，因为它主要存在于细胞外囊泡（EVs）中，可能来自单核细胞。我们得出结论，CoroMarker 是一种稳定、敏感和特异性的 CAD 生物标志物。
