Background. 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. Methods. 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. Results. 355 circRNAs were differentially expressed between these two groups: 164 were upregulated, and 191 were downregulated. Here, we selected the potential circRNAs (, ) as candidate biomarkers for further validation. Our data showed that only hsa_circ_0005540 was significantly associated with CAD (). After adjustment for risk factors, hsa_circ_0005540 showed a high discriminatory power for CAD in ROC analyses (; , ). Conclusion. Our results suggest that plasma exosomal hsa_circ_0005540 can be used as a promising diagnostic biomarker of CAD.

中文翻译：

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血浆衍生的外泌体环状 RNA hsa_circ_0005540 作为冠状动脉疾病的新型诊断生物标志物。

背景。外泌体几乎存在于所有体液中，含有多种可能反映疾病状态的生物成分。环状 RNA (circRNA) 结构稳定，在外泌体中半衰期长而不会降解，因此使其成为可靠的生物标志物。然而，外泌体 circRNA 作为冠状动脉疾病 (CAD) 生物标志物的潜力仍有待确定。在这里，我们旨在研究外泌体 circRNA 作为 CAD 诊断生物标志物的表达水平和潜在用途。方法. 使用 RNA 测序分析了从 CAD 患者的三个血浆样本和三个配对对照获得的外泌体中的 CircRNA 表达水平。然后在两中心验证队列中验证在分析阶段获得的外泌体 circRNA。最后，根据弗雷明汉心脏研究 (FHS) 风险因素调整后，外泌体 circRNA 的能力被确定为区分 CAD 患者和非 CAD 对照。结果。这两组之间有 355 个 circRNA 差异表达：164 个上调，191 个下调。在这里，我们选择了潜在的 circRNA (, )作为候选生物标志物进行进一步验证。我们的数据显示只有 hsa_circ_0005540 与 CAD 显着相关（）。在对风险因素进行调整后，hsa_circ_0005540 在 ROC 分析中显示出对 CAD 的高判别力（; , ）。 结论。我们的研究结果表明，血浆外泌体 hsa_circ_0005540 可用作 CAD 的有前途的诊断生物标志物。