血浆miRNA-21作为急性主动脉夹层分子标记物的初步探索
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摘要
目的通过急性主动脉夹层(AAD)病例对照研究分析血浆miR-21的相对表达水平,结合受试者工作曲线(ROC)及相关临床资料评估miR-21对AAD的诊断价值。方法收集华南地区汉族人群AAD 30例、心绞痛30例、急性心肌梗死(AMI) 29例及对照组29例样本,同时对各组样本的相关临床资料进行收集。通过实时荧光定量反转录聚合酶联反应分别检测各组血浆miR-21及内参基因miR-16表达水平,计算miR-21的相对表达量。结果与对照组比较,AAD组患者血浆miR-21的相对表达水平显著升高(P<0.05)。心绞痛组、AMI组与AAD组比较,血浆miR-21的表达水平差异无统计学意义(P>0.05)。ROC曲线分析显示曲线下面积(AUC)为0.664,95%置信区间为0.520～0.809,血浆miR-21对AAD诊断的敏感度为40%,特异度为96.6%。当miR-21相对表达量为0.034时,血浆miR-21对AAD诊断的敏感度为80%,特异度为20.7%。结论血浆miR-21检测对AAD的诊断具有一定的临床价值,但尚不足以支持其独立作为AAD理想的分子诊断标志物。
Aim Detection of relative expression levels of plasma miR-21 by a case-control study of acute aortic dissection( AAD),combined with receiver operating curve( ROC) and related clinical data to evaluate the diagnostic value of miR-21 for AAD. Methods 30 samples of AAD patients,30 samples of angina patients,29 patients with acute myocardial infarction( AMI) and 29 patients in the control group,clinical data of each group were also collected.The plasma levels of miR-21 and housekeeping gene miR-16 in each group were identified by quantitative reverse transcriptase polymerase amplification reaction,and the relative expression of miR-21 was calculated. Results Compared with the control group,the relative expression level of miR-21 in plasma of AAD group were significantly increased( P<0. 05). There was no significant difference in plasma miR-21 expression between angina pectoralis group vs AAD group and AMI group vs AAD group( P>0.05). ROC curve analysis showed that the area under the curve( AUC) was 0.664.The 95% confidence interval was 0.520 ～ 0.809,and the sensitivity of plasma miR-21 to AAD diagnosis was 40%,and the specificity was 96.6%. When the comparative expression of miR-21 was 0.034,the sensitivity of plasma miR-21 to AAD diagnosis was 80%,and the specificity was 20.7%. Conclusion The detection of plasma miR-21 has definite clinical value for the diagnosis of AAD,but it is not enough to support miR-21 as an ideal molecular diagnostic marker for AAD.
Aim Detection of relative expression levels of plasma miR-21 by a case-control study of acute aortic dissection( AAD),combined with receiver operating curve( ROC) and related clinical data to evaluate the diagnostic value of miR-21 for AAD. Methods 30 samples of AAD patients,30 samples of angina patients,29 patients with acute myocardial infarction( AMI) and 29 patients in the control group,clinical data of each group were also collected.The plasma levels of miR-21 and housekeeping gene miR-16 in each group were identified by quantitative reverse transcriptase polymerase amplification reaction,and the relative expression of miR-21 was calculated. Results Compared with the control group,the relative expression level of miR-21 in plasma of AAD group were significantly increased( P<0. 05). There was no significant difference in plasma miR-21 expression between angina pectoralis group vs AAD group and AMI group vs AAD group( P>0.05). ROC curve analysis showed that the area under the curve( AUC) was 0.664.The 95% confidence interval was 0.520 ～ 0.809,and the sensitivity of plasma miR-21 to AAD diagnosis was 40%,and the specificity was 96.6%. When the comparative expression of miR-21 was 0.034,the sensitivity of plasma miR-21 to AAD diagnosis was 80%,and the specificity was 20.7%. Conclusion The detection of plasma miR-21 has definite clinical value for the diagnosis of AAD,but it is not enough to support miR-21 as an ideal molecular diagnostic marker for AAD.
引文
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[17]Huang X,Yue Z,Wu J,et al.MicroRNA-21 knockout exacerbates angiotensin ii-induced thoracic aortic aneurysm and dissection in mice with abnormal transforming growth factor-β-SMAD3 signaling[J].Arterioscler Thromb Vasc Biol,2018,38(5):1086-1101.
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[20]Sheedy FJ,Palsson-McDermott E,Hennessy EJ,et al.Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21[J].Nat Immunol,2010,11(2):141-147.
[21]Zhou J,Wang KC,Wu W,et al.MicroRNA-21 targets peroxisome proliferators-activated receptor-αin an autoregulatory loop to modulate flow-induced endothelial inflammation[J].Proc Natl Acad Sci USA,2011,108(25):10355-10360.
[2]Hagan PG,Nienaber CA,Isselbacher EM,et al.The international registry of acute aortic dissection(irad):new insights into an old disease[J].JAMA,2000,283(7):897-903.
[3]Khvorova A,Reynolds A,Jayasena SD.Functional siRNAs and miRNAs exhibit strand bias[J].Cell,2003,115(2):209-216.
[4]Eldh M,Ekstrom K,Valadi H,et al.Exosomes communicate protective messages during oxidative stress,possible role of exosomal shuttle RNA[J].PLoS One,2010,5(12):e15353.
[5]Prokopi M,Pula G,Mayr U,et al.Proteomic analysis reveals presence of platelet micro-particles in endothelial progenitor cell cultures[J].Blood,2009,114(3):723-732.
[6]Zernecke A,Bidzhekov K,Noels H,et al.Delivery of microrna-126 by apoptotic bodies induces cxcl12-dependent vascular protection[J].Sci Signal,2009,2(100):ra81.
[7]Vickers KC,Palmisano BT,Shoucri BM,et al.MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins[J].Nat Cell Biol,2011,13(4):423-433.
[8]Yamakuchi M.MicroRNAs in vascular biology[J].Int JVasc Med,2012:794898
[9]Thum T,Gross C,Fiedler J,et al.MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts[J].Nature,2008,456(7224):980-984.
[10]Zhu SB,Zhu J,Zhou ZZ,et al.TGF-β1 induces human aortic vascular smooth muscle cell phenotype switch through PI3K/AKT/ID2 signaling[J].Am J Transl Res,2015,7(12):2764-2774.
[11]Cheng Y,Liu X,Zhang S,et al.MicroRNA-21 protects against the H2O2-induced injury on cardiac myocytes via its target gene PDCD4[J].J Mol Cell Cardiol,2009,47(1):5-14.
[12]Lin Y,Liu X,Cheng Y,et al.Involvement of MicroRNAs in hydrogen peroxide-mediated gene regulation and cellular injury response in vascular smooth muscle cells[J].J Biol Chem,2009,284(12):7903-7913.
[13]Xu Z,Wang Q,Pan J,et al.Characterization of serum miRNAs as molecular biomarkers for acute Stanford type A aortic dissection diagnosis[J].Sci Rep,2017,7(1):13659.
[14]Zhang XY,Shen BR,Zhang YC.et al.Induction of thoracic aortic remodeling by endothelial-specific deletion of microrna-21 in mice[J].PLoS One,2013,8(3):e59002.
[15]Luo M,Tan X,Mu L,et al.MiRNA-21 mediates the antiangiogenic activity of metformin through targeting PTENand SMAD7 expression and PI3K/AKT pathway[J].Sci Rep,2017,7:43427.
[16]Yuan J,Chen H,Ge D,et al.Mir-21 promotes cardiac fibrosis after myocardial infarction via targeting smad7[J].Cell Physiol Biochem,2017,42(6):2207-2219.
[17]Huang X,Yue Z,Wu J,et al.MicroRNA-21 knockout exacerbates angiotensin ii-induced thoracic aortic aneurysm and dissection in mice with abnormal transforming growth factor-β-SMAD3 signaling[J].Arterioscler Thromb Vasc Biol,2018,38(5):1086-1101.
[18]Canfrán-Duque A,Rotllan N,Zhang X,et al.Macrophage deficiency of miR-21 promotes apoptosis,plaque necrosis,and vascular inflammation during atherogenesis[J].EMBOMol Med,2017,9(9):1244-1262.
[19]Fan X,Wang E,Wang X,et al.MicroRNA-21 is a unique signature associated with coronary plaque instability in humans by regulating matrix metalloproteinase-9 via reversion-inducing cysteine-rich protein with Kazal motifs[J].Exp Mol Pathol,2014,96(2):242-249.
[20]Sheedy FJ,Palsson-McDermott E,Hennessy EJ,et al.Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21[J].Nat Immunol,2010,11(2):141-147.
[21]Zhou J,Wang KC,Wu W,et al.MicroRNA-21 targets peroxisome proliferators-activated receptor-αin an autoregulatory loop to modulate flow-induced endothelial inflammation[J].Proc Natl Acad Sci USA,2011,108(25):10355-10360.