循环 microRNAs 生物标志物panel 用于非侵入性诊断冠心病的鉴定:病例对照研究。
Identification of a circulating microRNAs biomarker panel for non-invasive diagnosis of coronary artery disease: case-control study.
机构信息
Medical Genetics Unit, Department of Histology and Cell Biology, Faculty of Medicine, Suez Canal University, Ismailia, 41522, Egypt.
Center of Excellence in Molecular & Cellular Medicine, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
出版信息
BMC Cardiovasc Disord. 2022 Jun 24;22(1):286. doi: 10.1186/s12872-022-02711-9.
BACKGROUND
Circulating microRNAs (miRNAs) are considered a hot spot of research that can be employed for monitoring and/or diagnostic purposes in coronary artery disease (CAD). Since different disease features might be reflected on altered profiles or plasma miRNAs concentrations, a combination of miRNAs can provide more reliable non-invasive biomarkers for CAD.
SUBJECTS AND METHODS
We investigated a panel of 14-miRNAs selected using bioinformatics databases and current literature searching for miRNAs involved in CAD using quantitative real-time PCR technique in 73 CAD patients compared to 73 controls followed by function and pathway enrichment analysis for the 14-miRNAs.
RESULTS
Our results revealed three out of the 14 circulating miRNAs understudy; miRNAs miR133a, miR155 and miR208a were downregulated. While 11 miRNAs were up-regulated in a descending order from highest fold change to lowest: miR-182, miR-145, miR-21, miR-126, miR-200b, miR-146A, miR-205, miR-135b, miR-196b, miR-140b and, miR-223. The ROC curve analysis indicated that miR-145, miR-182, miR-133a and, miR-205 were excellent biomarkers with the highest AUCs as biomarkers in CAD. All miRNAs under study except miR-208 revealed a statistically significant relation with dyslipidemia. MiR-126 and miR-155 showed significance with BMI grade, while only miR-133a showed significance with the obese patients in general. MiR-135b and miR-140b showed a significant correlation with the Wall Motion Severity Index. Pathway enrichment analysis for the miRNAS understudy revealed pathways relevant to the fatty acid biosynthesis, ECM-receptor interaction, proteoglycans in cancer, and adherens junction.
CONCLUSION
The results of this study identified a differentially expressed circulating miRNAs signature that can discriminate CAD patients from normal subjects. These results provide new insights into the significant role of miRNAs expression associated with CAD pathogenesis.
背景
循环 microRNAs(miRNAs)被认为是一个研究热点,可用于监测和/或诊断冠状动脉疾病(CAD)。由于不同的疾病特征可能反映在改变的 miRNA 谱或血浆 miRNA 浓度上,因此 miRNA 的组合可以为 CAD 提供更可靠的非侵入性生物标志物。
受试者和方法
我们使用生物信息学数据库和当前文献搜索选择了一组 14 个 miRNA,使用定量实时 PCR 技术在 73 例 CAD 患者中进行了研究,与 73 例对照相比,然后对 14 个 miRNA 进行功能和途径富集分析。
结果
我们的结果显示,在研究的 14 个循环 miRNA 中有 3 个miRNA下调;miR133a、miR155 和 miR208a。而在从最高倍数变化到最低倍数的 11 个 miRNA 中,miR-182、miR-145、miR-21、miR-126、miR-200b、miR-146A、miR-205、miR-135b、miR-196b、miR-140b 和 miR-223 呈上调趋势。ROC 曲线分析表明,miR-145、miR-182、miR-133a 和 miR-205 作为 CAD 的生物标志物具有最高 AUC,是优秀的生物标志物。除 miR-208 外,所有研究的 miRNA 均与血脂异常呈统计学显著相关。miR-126 和 miR-155 与 BMI 分级有显著意义,而仅 miR-133a 与肥胖患者有显著意义。miR-135b 和 miR-140b 与壁运动严重程度指数有显著相关性。对研究中的 miRNAS 进行途径富集分析表明,与脂肪酸生物合成、ECM-受体相互作用、癌症中的蛋白聚糖和黏着连接相关的途径具有重要意义。
结论
本研究确定了一个可区分 CAD 患者和正常受试者的差异表达循环 miRNA 特征。这些结果为 miRNA 表达与 CAD 发病机制的显著作用提供了新的见解。