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[血清微小RNA联合检测在急性主动脉夹层早期诊断中的价值]

[The value of serum microRNA combined detection for early diagnosis of acute aortic dissection].

作者信息

Liu X Y, Zhang D, Zhao X, Aizezi Ayitila, Ma X

机构信息

State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia,Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China.

出版信息

Zhonghua Xin Xue Guan Bing Za Zhi. 2025 Apr 24;53(4):394-401. doi: 10.3760/cma.j.cn112148-20250303-00156.

Abstract

To investigate the value of serum microRNA (miRNA) levels in the early diagnosis of acute aortic dissection (AAD). (1) Human umbilical vein endothelial cells (HUVEC) were transfected with hsa-miR-744-5p mimic and its negative control mimic, and cell proliferation and migration were assessed using the CCK-8 assay and wound healing assay. (2) A total of 40 patients diagnosed with AAD by whole-aorta CT angiography in the Emergency Department of the First Affiliated Hospital of Xinjiang Medical University from January 2020 to January 2022 were enrolled as the AAD group. The time interval between chest pain onset and blood sample collection was less than 24 hours. Meanwhile, 40 age- and sex-matched healthy individuals undergoing routine physical examinations were selected as the control group. The initial blood samples were collected from AAD patients upon admission, while fasting blood samples were collected from the control group. Based on our previous research findings, the top 10 miRNAs with the highest fold-change (>1) and the most significant upregulation were identified. Through a literature review, three miRNAs (miR-206, miR-143-3p, and miR-744-5p) were selected as target miRNAs. Laboratory test results, including D-dimer levels, were collected from both groups. The relative expression levels of target miRNAs in both groups were measured using quantitative real-time polymerase chain reaction (qRT-PCR). Spearman correlation analysis was performed to assess the correlation of target miRNA expression levels. Receiver operating characteristic (ROC) curves were plotted to calculate the area under the curve (), sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy. (1) The CCK-8 assay showed that compared with HUVEC transfected with negative control mimic, HUVEC transfected with hsa-miR-744-5p exhibited lower absorbance values at all time points (all <0.05). The wound healing assay indicated that the relative migration rate of HUVEC transfected with hsa-miR-744-5p mimic was significantly lower (<0.05). (2) The D-dimer level significantly differed between the AAD group and the control group (1 737.0 (660.5, 3 297.5) μg/L vs. 66.0 (34.0, 89.0) μg/L, <0.001). The expression levels of all three miRNA in the serum of AAD patients were significantly upregulated compared with the control group by qRT-PCR (all <0.05). Spearman correlation analysis revealed positive correlations between miR-206 and miR-744-5p (=0.508, <0.001), miR-143-3p and miR-744-5p (=0.695, <0.001), and miR-206 and miR-143-3p (=0.651, <0.001). All three miRNAs had diagnostic value for AAD in ROC analysis, with miR-206 demonstrating the highest diagnostic accuracy (67.50%) and a specificity of 92.5%. The combined detection of miRNA improved diagnostic accuracy, with miR-206+miR-143-3p achieving an accuracy of 71.25%, specificity of 100%, and positive predictive value of 100%. The combination of miRNA with D-dimer further enhanced diagnostic accuracy, with miR-206+miR-744-5p+D-dimer achieving the highest accuracy (97.50%), along with sensitivity, specificity, positive predictive value, and negative predictive value all at 97.5%. The diagnostic performance of miR-206+miR-143-3p+miR-744-5p+D-dimer was identical to that of miR-206+miR-744-5p+D-dimer. miR-206, miR-143-3p, and miR-744-5p show great potential for the early diagnosis of acute aortic dissection, and their combination with D-dimer can significantly improve diagnostic sensitivity, specificity and accuracy.

摘要

探讨血清微小RNA(miRNA)水平在急性主动脉夹层(AAD)早期诊断中的价值。(1)将hsa-miR-744-5p模拟物及其阴性对照模拟物转染到人脐静脉内皮细胞(HUVEC)中,采用CCK-8法和伤口愈合试验评估细胞增殖和迁移。(2)选取2020年1月至2022年1月在新疆医科大学第一附属医院急诊科经全主动脉CT血管造影诊断为AAD的40例患者作为AAD组。胸痛发作至采血的时间间隔小于24小时。同时,选取40例年龄、性别匹配的接受常规体检的健康个体作为对照组。AAD患者入院时采集初始血样,对照组采集空腹血样。根据我们之前的研究结果,确定了变化倍数最高(>1)且上调最显著的前10个miRNA。通过文献回顾,选择了3个miRNA(miR-206、miR-143-3p和miR-744-5p)作为目标miRNA。收集两组的实验室检测结果,包括D-二聚体水平。采用定量实时聚合酶链反应(qRT-PCR)检测两组中目标miRNA的相对表达水平。进行Spearman相关性分析以评估目标miRNA表达水平的相关性。绘制受试者工作特征(ROC)曲线,计算曲线下面积()、敏感性、特异性、阳性预测值、阴性预测值和诊断准确性。(1)CCK-8试验显示,与转染阴性对照模拟物的HUVEC相比,转染hsa-miR-744-5p的HUVEC在所有时间点的吸光度值均较低(均<0.05)。伤口愈合试验表明,转染hsa-miR-744-5p模拟物的HUVEC的相对迁移率显著降低(<0.05)。(2)AAD组和对照组的D-二聚体水平差异显著(1737.0(660.5,3297.5)μg/L对66.0(34.0,89.0)μg/L,<0.001)。qRT-PCR显示,AAD患者血清中所有3种miRNA的表达水平均较对照组显著上调(均<0.05)。Spearman相关性分析显示,miR-206与miR-744-5p之间呈正相关(=0.508,<0.001),miR-143-3p与miR-744-5p之间呈正相关(=0.695,<0.001),miR-206与miR-143-3p之间呈正相关(=0.651,<0.001)。在ROC分析中,所有3种miRNA对AAD均具有诊断价值,其中miR-206的诊断准确性最高(67.50%),特异性为92.5%。miRNA联合检测提高了诊断准确性,miR-206+miR-143-3p的准确性为71.25%,特异性为100%,阳性预测值为100%。miRNA与D-二聚体联合进一步提高了诊断准确性,miR-206+miR-744-5p+D-二聚体的准确性最高(97.50%),敏感性、特异性、阳性预测值和阴性预测值均为97.5%。miR-206+miR-143-3p+miR-744-5p+D-二聚体的诊断性能与miR-206+miR-744-5p+D-二聚体相同。miR-206、miR-143-3p和miR-744-5p在急性主动脉夹层的早期诊断中显示出巨大潜力,它们与D-二聚体联合可显著提高诊断敏感性、特异性和准确性。

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