急性冠脉综合征早期差异蛋白及其特异性和敏感性的研究(1)
【摘要】目的 应用蛋白质谱技术对早期急性冠脉综合征患者的血清进行检测，从中筛选出特异性和敏感性均高的早期急性冠脉综合征特别是不稳定心绞痛的差异蛋白，为早期诊断不稳定心绞痛提供特异性诊断方法。方法 选择发病4 h内急性冠脉综合征患者血清标本31份，其中不稳定心绞痛12例，非ST段抬高急性心肌梗死5例，ST段抬高急性心肌梗死14例；对照组30例来自体检患者，性别、年龄、高血压、冠心病等病史与实验组相匹配。磁珠分离血清蛋白，飞行时间质谱分析仪收集蛋白质荷比为0～50 000的数据进行分析；将筛选出的差异显著的蛋白与目前常用的心肌损伤、心肌缺血和炎症反应标志物进行特异性和敏感性对比。结果 (1)发现3个差异极为显著的蛋白，质荷比分别为3167、4183、4292，ACS组和对照组的蛋白质表达量分别为(8.2612±2.94)vs.(2.1430±1.45)，P=2×10-10；(19.6203±16.14)vs.(2.8844±2.26)，P=4×10-10；(13.5229±10.36)vs.(1.8642±1.07)，P=0。(2)3个差异蛋白与心脏型脂肪酸结合蛋白、髓过氧化物酶进行特异性与敏感性对比研究，无论是诊断急性冠脉综合征，还是分别诊断不稳定心绞痛和急性心肌梗死，3个差异蛋白ROC曲线下面积均为最大，分别为0.976～0.989、0.967～0.988、0.992～1.0，而高敏C反应蛋白及缺血修饰白蛋白经t检验在ACS组与对照组之间差异无统计学意义(P>0.05)。结论 3个差异蛋白有可能是新的早期急性冠脉综合征特别是不稳定心绞痛的生物标记物。
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【关键词】急性冠脉综合征；不稳定心绞痛；早期诊断；蛋白组学；小分子生物标记物；辅助激光解析离子化飞行时间质谱
The specificity and sensitivity of differential proteins detected for diagnosis in the early stage of acute coronary syndrome XIA Hu， ZHANG Jun， LIU Li-feng， SONG Hai-jing， FENG Kai， FAN Xiao-dong， QIAO Li， JIN Shan， LU Hao-jun. Emergency Departmeng， The 306th Hospital of PLA， Beijing 100101，China
Corresponding author： XIA Hu，Email： xiahu306@163.com
, 百拇医药
【Abstract】Objective To explore an early diagnosis method for identifying the unstable angina(UA) patients. The concentration of proteins in patient serums and the differential proteins with high specificity and sensitivity selected to determine the early stage of acute coronary syndrome (ACS) in patients especially with UA was deteced by using protein mass spectrometry technology. Method A total of 31 samples of patient serum within 4 h after ACS symptoms emerged were selected including 12 patients with UA， 5 with non-ST-segment elevation acute myocardial infarctions (NSTEMI) and 14 with ST-segment elevation acute myocardial infarctions(STEMI). Another 30 serum samples from the subjects asking for physical examination with the gender， age， past histories such as hypertension and coronary heart diseases comparable to the ACS patients were selected as control group. The serum proteins were obtained by magnetic bead separation technique and the data with mass-to-charge ratio between 0 and 50 000 obtained from time-of-flight mass spectrometer were analyzed. The specificity and sensitivity of proteins with prominent differential in ACS patient serums were compared with those of the commonly utilized inflammatory reaction markers and myocardial injury or ischemia markers. Results Three differential proteins with the significantly higher concentration in serums were found with the mass-to-charge ratio of 3167， 4183 and 4292 respectively (protein expression was (8.2612±2.94) vs.(2.1430±1.45)，P=2×10-10；(19.6203±16.14) vs.(2.8844±2.26)，P=4×10-10；(13.5229±10.36) vs.(1.8642±1.07)，P=0，compared to the control group respectively). These three differential proteins also accounted for the largest area under receiver operating characteristics (ROC) curve in diagnosis ACS， UA and AMI (that was 0.976-0.989，0.967-0.988，0.992-1.0 respectively)compared with heart type fatty acid binding protein (H-FABP) and myeloperoxidase (MPO)， while there was no statistically significantly difference in high-sensitive C reactive protein (hs-CRP) and Ischemia-modified albumin (IMA) between two groups(P>0.05). Conclusions These three differential proteins might be the novel biomarkers for diagnosis in the early stage of ACS， especially UA.
, http://www.100md.com(夏鹄 张军 刘利峰 宋海晶 冯凯 樊晓东 乔莉 金珊 路浩军)
, http://www.100md.com
【关键词】急性冠脉综合征；不稳定心绞痛；早期诊断；蛋白组学；小分子生物标记物；辅助激光解析离子化飞行时间质谱
The specificity and sensitivity of differential proteins detected for diagnosis in the early stage of acute coronary syndrome XIA Hu， ZHANG Jun， LIU Li-feng， SONG Hai-jing， FENG Kai， FAN Xiao-dong， QIAO Li， JIN Shan， LU Hao-jun. Emergency Departmeng， The 306th Hospital of PLA， Beijing 100101，China
Corresponding author： XIA Hu，Email： xiahu306@163.com
, 百拇医药
【Abstract】Objective To explore an early diagnosis method for identifying the unstable angina(UA) patients. The concentration of proteins in patient serums and the differential proteins with high specificity and sensitivity selected to determine the early stage of acute coronary syndrome (ACS) in patients especially with UA was deteced by using protein mass spectrometry technology. Method A total of 31 samples of patient serum within 4 h after ACS symptoms emerged were selected including 12 patients with UA， 5 with non-ST-segment elevation acute myocardial infarctions (NSTEMI) and 14 with ST-segment elevation acute myocardial infarctions(STEMI). Another 30 serum samples from the subjects asking for physical examination with the gender， age， past histories such as hypertension and coronary heart diseases comparable to the ACS patients were selected as control group. The serum proteins were obtained by magnetic bead separation technique and the data with mass-to-charge ratio between 0 and 50 000 obtained from time-of-flight mass spectrometer were analyzed. The specificity and sensitivity of proteins with prominent differential in ACS patient serums were compared with those of the commonly utilized inflammatory reaction markers and myocardial injury or ischemia markers. Results Three differential proteins with the significantly higher concentration in serums were found with the mass-to-charge ratio of 3167， 4183 and 4292 respectively (protein expression was (8.2612±2.94) vs.(2.1430±1.45)，P=2×10-10；(19.6203±16.14) vs.(2.8844±2.26)，P=4×10-10；(13.5229±10.36) vs.(1.8642±1.07)，P=0，compared to the control group respectively). These three differential proteins also accounted for the largest area under receiver operating characteristics (ROC) curve in diagnosis ACS， UA and AMI (that was 0.976-0.989，0.967-0.988，0.992-1.0 respectively)compared with heart type fatty acid binding protein (H-FABP) and myeloperoxidase (MPO)， while there was no statistically significantly difference in high-sensitive C reactive protein (hs-CRP) and Ischemia-modified albumin (IMA) between two groups(P>0.05). Conclusions These three differential proteins might be the novel biomarkers for diagnosis in the early stage of ACS， especially UA.
, http://www.100md.com(夏鹄 张军 刘利峰 宋海晶 冯凯 樊晓东 乔莉 金珊 路浩军)