血浆循环microRNA-30d在急性冠状动脉综合征中应用的初探

摘要

目的 评估血浆循环microRNA-30d(miR-30d)在急性冠状动脉综合征(ACS)患者早期诊断及预后中的应用价值.方法 收集2011年9月至2012年12月期间泰达国际心血管病医院急诊科入院的170例ACS患者,其中ST段抬高型心肌梗死(STEMI)70例(男54例,女16例)、非ST段抬高型心肌梗死(NSTEMI)52例(男34例,女18例)、不稳定心绞痛(UAP)患者48例(男29例,女19例);同期收集该院健康服务部的体检者41名(男24名,女17名)作为对照组;通过定量逆转录聚合酶链反应(qRT-PCR)检测血浆中miR-30d的相对表达量.在20例急性心肌梗死(AMI)患者胸痛发作后0~3 h、4~6 h、7~9 h、10~12 h及13~24 h的连续时间点血浆样本中,比较miR-30d相对表达量与心肌肌钙蛋白I(cTnI)、肌红蛋白(Myo)等其他标志物浓度的动态变化;同时应用ROC曲线下面积和Kaplan-Meier生存曲线分析评估miR-30d在ACS中的应用价值.结果 胸痛发作0 ~3 h内, STEMI、NSTEMI患者血浆中miR-30d的相对表达水平分别为7.208(0.170 ~11070.735)和7.989 (0.836~151.391),均较对照组1.561(0.044 ~17.520)升高(Z1 =-5.792,Z2 =-6.113,P均<0.001),UAP组1.073(0.051~11.095)与对照组之间差异无统计学意义(Z=-0.325, P=0.745);20例AMI患者中,miR-30d相对表达量在胸痛发作后0~3 h开始升高、4~6 h达到峰值、7~9 h开始下降,时间均早于cTnI,且与其浓度变化正相关(r=0.402,P<0.01);胸痛发作0~3 h内,miR-30 d诊断AMI的ROC曲线下面积(AUC)为0.882(95% CI:0.830~0.935),灵敏度为0.795(95% CI:0.711~0.861)、特异度为0.854(95% CI:0.716 ~0.935);联合miR-30d与 cTnI 后,AUC(0.937, 95%CI:0.902~0.972)及特异度(0.937,95% CI:0.818~0.984)均明显提高;Kaplan-Meier生存曲线分析显示0~3 h内的miR-30d水平与AMI患者30天(30 d)及12个月心脏主要不良事件(MACE)无关(30 d:χ2=0.506,P=0.477;12个月:χ2=0.002,P=0.963).结论 血浆循环miR-30d相对表达水平的升高早于cTnI,可能为早期诊断ACS的分子标志物,但不能用于AMI患者短、长期预后的评估.%Objective To investigate the diagnosis and prognosis value of plasma microRNA-30d (miR-30d)in acute coronary syndrome(ACS)patients.Methods It retrospectively recruited 170 cases of ACS patients from TEDA International Cardiovascular Hospital between September 2011 to February 2012, including 70 STEMI(male 54,female 16), 52 NSTEMI(male 34,female 18),48 UAP(male 29,female 19).At the same time,41 healthy controls(male 24,female 17)were enrolled into the study.Plasma miR-30d levels were determined by real-time quantitative PCR.In order to evaluate the dynamic change of miR-30d and other cardiac biomarkers,20 plasma samples of AMI patients were collected at 0-3 h,4-6 h,7-9 h, 10-12 h after pectoralgia.ROC curves and Kaplan-Meier survival curve were used to investigate clinical value of miR-30d in ACS.Results At 0-3 h after pectoralgia, miR-30d were significant higher in STEMI 7.208(0.170-11 070.735)and NSTEMI 7.989(0.836-151.391)than the controls 1.561(0.044-17.520)（Z1＝-5.792,Z2 ＝-6.113,P＜0.001）, but there were no statistic differences between UAP 1.073 （0.051-11.095）patients and the controls（Z＝-0.325,P＝0.745）.In 20 AMI patients,miR-30d levels peaked at 4-6 h and then dropped following 7-9 h, both earlier than cTnI, and the variation tendency was positive correlated with cTnI（r＝0.402,P＜0.01）.At 0-3 h after pectoralgia, the AUC, sensitivity and specificity of miR-30d for differentiating AMI and UAP were 0.882（95％ CI:0.830-0.935）,0.795（95％CI:0.711-0.861）and 0.854（95％ CI:0.716-0.935）respectively.When combined miR-30d and cTnI, the diagnostic AUC and specificity were 0.937（95％ CI: 0.902-0.972）and 0.937（95％ CI:0.818-0.984）,both enhanced when compared with miR-30d or cTnI alone.Kaplan-Meier survival curves revealed that there were no significant correlations between the miR-30d levels and MACE in both 30 days and 12 months（χ$lt@span sup=1$gt@2$lt@/span$gt@＝0.506,P＝0.477 and χ$lt@span sup=1$gt@2$lt@/span$gt@＝0.002, P＝0.963 respectively）.Conclusion Plasma miR-30d may be used as a potential biomarker for early diagnosis, but not prognosis in ACS patients.