Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Institute of Aging Research, Guangdong Medical University, Dongguan 523808, China.
Institute of Biochemistry & Molecular Biology, Guangdong Medical University, Zhanjiang 524023, China.
Dis Markers. 2020 Jun 30;2020:3178642. doi: 10.1155/2020/3178642. eCollection 2020.
Exosomes exist in almost all body fluid and contain diverse biological contents which may be reflective of disease state. Circular RNAs (circRNAs) are stable in structure and have a long half-life in exosomes without degradation, thus making them reliable biomarkers. However, the potential of exosomal circRNAs as biomarkers of coronary artery disease (CAD) remains to be established. Here, we aimed to investigate the expression levels and the potential use of exosomal circRNAs as diagnostic biomarkers for CAD.
CircRNA expression levels in exosomes obtained from three plasma samples of CAD patients and three paired controls were analyzed using RNA sequencing. Exosomal circRNAs obtained in the profiling phase were then verified in two-center validation cohorts. Finally, the ability of exosomal circRNAs, adjusting for Framingham Heart Study (FHS) risk factors, was determined to discriminate between CAD patients and non-CAD controls.
355 circRNAs were differentially expressed between these two groups: 164 were upregulated, and 191 were downregulated. Here, we selected the potential circRNAs (fold change > 4, < 0.05) as candidate biomarkers for further validation. Our data showed that only hsa_circ_0005540 was significantly associated with CAD ( < 0.0001). After adjustment for risk factors, hsa_circ_0005540 showed a high discriminatory power for CAD in ROC analyses (AUC = 0.853; 95%confidence interval (CI) = 0.799 - 0.906, < 0.001).
Our results suggest that plasma exosomal hsa_circ_0005540 can be used as a promising diagnostic biomarker of CAD.
外泌体存在于几乎所有体液中，包含多种可能反映疾病状态的生物物质。环状 RNA（circRNA）结构稳定，在没有降解的情况下在 exosomes 中半衰期长，因此成为可靠的生物标志物。然而，外泌体 circRNA 作为冠心病（CAD）生物标志物的潜力尚未得到证实。在这里，我们旨在研究 exosomal circRNA 的表达水平及其作为 CAD 诊断生物标志物的潜在用途。
使用 RNA 测序分析来自 3 名 CAD 患者和 3 名配对对照的血浆样本中获得的外泌体中的 circRNA 表达水平。在鉴定阶段获得的外泌体 circRNA 然后在两个中心验证队列中进行验证。最后，确定外泌体 circRNA（调整 Framingham 心脏研究（FHS）危险因素后）区分 CAD 患者和非 CAD 对照组的能力。
这两组之间有 355 个 circRNA 表达差异：164 个上调，191 个下调。在这里，我们选择了潜在的 circRNA（倍数变化 > 4， < 0.05）作为进一步验证的候选生物标志物。我们的数据表明，只有 hsa_circ_0005540 与 CAD 显著相关（<0.0001）。调整危险因素后，hsa_circ_0005540 在 ROC 分析中对 CAD 具有较高的区分能力（AUC = 0.853；95%置信区间（CI）= 0.799-0.906， < 0.001）。
我们的结果表明，血浆外泌体 hsa_circ_0005540 可作为 CAD 的有前途的诊断生物标志物。
