动态监测外周血CPNE3对急性心肌梗死的诊断价值
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摘要
目的动态监测急性心肌梗死(AMI)患者外周血CPNE3基因表达,探讨其对AMI的早期诊断价值。方法将2016年7月～2017年7月于本院就诊的154例胸痛患者,按照AMI诊断标准分为AMI组48例和非AMI组106例,另选择60例健康人群作为对照组。AMI组分别于入院即刻、入院后4h、6h、12h、24h采集肘静脉血,非AMI组和对照组于入组时抽取静脉血,采用胶乳增强免疫比浊法检测血清c Tn I浓度,电化学发光法检测血清CK-MB含量,实时荧光定量PCR检测外周血CPNE3mRNA相对表达量;利用受试者工作曲线(ROC)计算CPNE3mRNA表达对AMI的早期诊断效能。结果与非AMI组和对照组比较,AMI组的吸烟比例、高血压和糖尿病发病率增加,TC、TG、LDL-C、CK-MB、cTnI升高,HDL-C降低,差异有统计学意义(P <0.05)。入院即刻AMI组外周血CPNE3mRNA表达明显低于非AMI组和对照组(P <0.05),非AMI组和对照组CPNE3mRNA表达的差异无统计学意义(P>0.05)。cTnI入院后6h达峰值,CK-MB在患者入院后12h达峰值,CPNE3mRNA在入院后4h降至最低值;与入院即刻比较,入院后各时段AMI组cTnI、CK-MB明显升高,CPNE3mRNA明显降低,差异有统计学意义(P <0.05)。CPNE3mRNA表达与cTnI呈负相关(r=–0.198,P=0.016),CPNE3mRNA表达与CK-MB也呈负相关(r=–0.227,P=0.029)。ROC曲线分析显示,CPNE3诊断AMI的ROC曲线下面积(AUC)为0.910,敏感度为97.9%,特异度为75.0%;cTnI的AUC为0.801,敏感度为68.7%,特异度为89.6%;CK-MB的AUC为0.912,敏感度为75.0%,特异度为95.8%。结论 CPNE3可作为早期诊断AMI的指标,其诊断效能优于cTnI,与CK-MB相当。实时荧光定量PCR检测外周血CPNE3时间短,可满足临床急诊需求。
Objective To detect the circulating CPNE3 mRNA in the patients with acute myocardial infarction for evaluation of its diagnostic potential. Methods A total of 154 patients who were suffering from chest pain were admitted to the hospital. The patients were divided into AMI group(4 8 cases) and non-AMI group(106 cases) according to the diagnostic criteria. Sixty healthy persons were taken as control. Vein blood of AMI patients was collected immediately on admission and 4h,6h,12h,24h after admission. The level of serum cTnI was detected by Latex particle-enhanced turbidimetric immunoassay and serum cTnI,by electrochemiluminescence. The circulating CPNE3 mRNAs were examined by qRT-PCR. Results Compared to the non-AMI or the control,AMI mostly occurred in the individuals of smoking,hypertension and diabetes with a high level of TC,TG,LDL-C,CK-MB,and cTnI and a low level of HDL-C(P <0.05).The CPNE3 mRNA in the AMI patients was significantly elevated(P <0.05) on immediate admission but greatly reduced at4 h after admission and no significant difference was noted between the non-AMI group and the control(P >0.05). The level of cTnI reached peak value at 6 h after admission and CK-MB,at 12 h after admission. The cTnI and CK-MB increased and CPNE3 mRNA remarkably decreased in AMI patients at different stages of admission(P <0.05). ROC curve analysis showed that the area under ROC curve(AUC) for the diagnostic value of CPNE3 mRNA on AMI was 0.910,with the sensitivity and specificity of 97.9% and 75.0%,respectively. The AUC for cTnI was 0.801,with the sensitivity and specificity of 68.7%and 8 9.6%. The AUC for CK-MB was 0.9 1 2,with the sensitivity and specificity of 7 5.0% and 9 5.8%. Conclusion The circulating CPNE3 mRNA has the potential in early diagnosis of AMI,which may be superior or equal to cTnI or CK-MB.
Objective To detect the circulating CPNE3 mRNA in the patients with acute myocardial infarction for evaluation of its diagnostic potential. Methods A total of 154 patients who were suffering from chest pain were admitted to the hospital. The patients were divided into AMI group(4 8 cases) and non-AMI group(106 cases) according to the diagnostic criteria. Sixty healthy persons were taken as control. Vein blood of AMI patients was collected immediately on admission and 4h,6h,12h,24h after admission. The level of serum cTnI was detected by Latex particle-enhanced turbidimetric immunoassay and serum cTnI,by electrochemiluminescence. The circulating CPNE3 mRNAs were examined by qRT-PCR. Results Compared to the non-AMI or the control,AMI mostly occurred in the individuals of smoking,hypertension and diabetes with a high level of TC,TG,LDL-C,CK-MB,and cTnI and a low level of HDL-C(P <0.05).The CPNE3 mRNA in the AMI patients was significantly elevated(P <0.05) on immediate admission but greatly reduced at4 h after admission and no significant difference was noted between the non-AMI group and the control(P >0.05). The level of cTnI reached peak value at 6 h after admission and CK-MB,at 12 h after admission. The cTnI and CK-MB increased and CPNE3 mRNA remarkably decreased in AMI patients at different stages of admission(P <0.05). ROC curve analysis showed that the area under ROC curve(AUC) for the diagnostic value of CPNE3 mRNA on AMI was 0.910,with the sensitivity and specificity of 97.9% and 75.0%,respectively. The AUC for cTnI was 0.801,with the sensitivity and specificity of 68.7%and 8 9.6%. The AUC for CK-MB was 0.9 1 2,with the sensitivity and specificity of 7 5.0% and 9 5.8%. Conclusion The circulating CPNE3 mRNA has the potential in early diagnosis of AMI,which may be superior or equal to cTnI or CK-MB.
引文
1 Paradela-Dobarro B, Raposeiras-Roubin S, RodinoJaneiro BK, et al.Statins modulate feedback regulation mechanisms between advanced glycation end-products and C-reactive protein:evidence in patients with acute myocardial infarction[J].Eur J Pharm Sci, 2013, 49(4):512-518.
2 Lin H C, Zhang F L, Geng Q, et al.Quantitative proteomic analysis identifies CPNE3 as a novel metastasis-promoting gene in NSCLC[J]. J Proteome Res, 2013, 12(7):3423-3433.
3程光嘉,刘顺林,王金志,等.CPNE3蛋白在肺腺癌组织中的表达及其临床意义[J].浙江医学,2016, 38(17):1436-1438.
4 Cohen O S, Mccoy S Y, Middleton F A, et al.Transcriptomic Analysis of Postmortem Brain identifies Dysregulated Splicing Events in Novel Candidate Genes for Schizop.hrenia[J]. Schizophr Res,2012, 142(1-3):188-199.
5王孟,谭卜川,杨玉双,等.外周血CPNE3表达异常可能作为评估稳定冠心病发展为急性心肌梗死的遗传标志[J].中国实验诊断学,2017, 21(9):1556-1561.
6 Heinrich C, Keller C, Boulay A, et al.Copine-Ⅲinteracts with ErbB2 and promotes tumor cell migration.[J]. Oncogene, 2010, 29(11):1598-1610.
7钟光珍,那开宪.全球心肌梗死统一定义指南解读[J].中国临床医生杂志,2009, 37(4):70-71.
8 Ghislat G, Knecht E.New Ca(~(2+))-dependent regulators of autophagosome maturation[J]. Commun Integr Biol,2012, 5(4):308-311.
9 Perestenko P V, Pooler A, Noorbakhshnia M, et al.Copines-1,-2,-3,-6 and-7 show different calciumdependent intracellular membrane translocation and targeting[J]. FEBS J, 2010, 277(24):5174-5189.
10 Li Y, Gou M, Sun Q,e t al.Requirement of calcium binding, myristoy lation, and proteinprotein interaction for the Copine BON1 function in Arabidopsis.[J]. J Biol Chem, 2010, 285(39):29884-29891.
11苏红英,黄雄飞,陈淑勤,等.钙依赖性磷脂结合蛋白Ⅱ在人胃腺癌组织中上调表达及其意义[J].中华实验外科杂志,2014, 31(7):1563-1565.
12汤祥瑞.急性心肌梗死和稳定型冠心病患者血清尾加压素Ⅱ和神经激肽B的变化[J].中国急救医学,2015, 35(6):526-529.
13范艳慧,戴瑞,蒲瑜,等.心肌梗死溶栓复流后血清标志物的变化及临床意义[J].中国急救医学,2015, 35(12):1112-1117.
14朱改针,李凌,卫世强,等.溶栓后时间优化经皮冠状动脉介人治疗青年心肌梗死与直接介人治疗的疗效比较[J].中华危重病急救医学,2016, 28(12):1148-1150.
15 Li C H, Chiang C P, Yang J Y, et al.RING-type ubiquitin ligase McCPNl catalyzes UBC8-dependent protein ubiquitination and interacts with Argonaute 4 in halophyte ice plant[J]. Plant Physiol Biochem, 2014,80(7):211-219.
16张能,张丹,张煜,等.高敏心肌肌钙蛋白Ⅰ动态变化在急性冠状动脉综合征早期诊断中的应用价值[J].中国循环杂志,2016, 31(1):25-30.
17苏彤,张晓璞,韩志君,等.循环微小RNA-1对胸痛患者发生急性心肌梗死的早期诊断价值[J].中华危重病急救医学,2016, 28(7):607-611.
18 Perestenko P, Watanabe M, Beusnard-Bee T, et al.The second C2-domain of copine-2, copine-6 and copine-7is responsible for their calcium-dependent membrane association[J]. FEBS J, 2015, 282(19):3722-3736.
2 Lin H C, Zhang F L, Geng Q, et al.Quantitative proteomic analysis identifies CPNE3 as a novel metastasis-promoting gene in NSCLC[J]. J Proteome Res, 2013, 12(7):3423-3433.
3程光嘉,刘顺林,王金志,等.CPNE3蛋白在肺腺癌组织中的表达及其临床意义[J].浙江医学,2016, 38(17):1436-1438.
4 Cohen O S, Mccoy S Y, Middleton F A, et al.Transcriptomic Analysis of Postmortem Brain identifies Dysregulated Splicing Events in Novel Candidate Genes for Schizop.hrenia[J]. Schizophr Res,2012, 142(1-3):188-199.
5王孟,谭卜川,杨玉双,等.外周血CPNE3表达异常可能作为评估稳定冠心病发展为急性心肌梗死的遗传标志[J].中国实验诊断学,2017, 21(9):1556-1561.
6 Heinrich C, Keller C, Boulay A, et al.Copine-Ⅲinteracts with ErbB2 and promotes tumor cell migration.[J]. Oncogene, 2010, 29(11):1598-1610.
7钟光珍,那开宪.全球心肌梗死统一定义指南解读[J].中国临床医生杂志,2009, 37(4):70-71.
8 Ghislat G, Knecht E.New Ca(~(2+))-dependent regulators of autophagosome maturation[J]. Commun Integr Biol,2012, 5(4):308-311.
9 Perestenko P V, Pooler A, Noorbakhshnia M, et al.Copines-1,-2,-3,-6 and-7 show different calciumdependent intracellular membrane translocation and targeting[J]. FEBS J, 2010, 277(24):5174-5189.
10 Li Y, Gou M, Sun Q,e t al.Requirement of calcium binding, myristoy lation, and proteinprotein interaction for the Copine BON1 function in Arabidopsis.[J]. J Biol Chem, 2010, 285(39):29884-29891.
11苏红英,黄雄飞,陈淑勤,等.钙依赖性磷脂结合蛋白Ⅱ在人胃腺癌组织中上调表达及其意义[J].中华实验外科杂志,2014, 31(7):1563-1565.
12汤祥瑞.急性心肌梗死和稳定型冠心病患者血清尾加压素Ⅱ和神经激肽B的变化[J].中国急救医学,2015, 35(6):526-529.
13范艳慧,戴瑞,蒲瑜,等.心肌梗死溶栓复流后血清标志物的变化及临床意义[J].中国急救医学,2015, 35(12):1112-1117.
14朱改针,李凌,卫世强,等.溶栓后时间优化经皮冠状动脉介人治疗青年心肌梗死与直接介人治疗的疗效比较[J].中华危重病急救医学,2016, 28(12):1148-1150.
15 Li C H, Chiang C P, Yang J Y, et al.RING-type ubiquitin ligase McCPNl catalyzes UBC8-dependent protein ubiquitination and interacts with Argonaute 4 in halophyte ice plant[J]. Plant Physiol Biochem, 2014,80(7):211-219.
16张能,张丹,张煜,等.高敏心肌肌钙蛋白Ⅰ动态变化在急性冠状动脉综合征早期诊断中的应用价值[J].中国循环杂志,2016, 31(1):25-30.
17苏彤,张晓璞,韩志君,等.循环微小RNA-1对胸痛患者发生急性心肌梗死的早期诊断价值[J].中华危重病急救医学,2016, 28(7):607-611.
18 Perestenko P, Watanabe M, Beusnard-Bee T, et al.The second C2-domain of copine-2, copine-6 and copine-7is responsible for their calcium-dependent membrane association[J]. FEBS J, 2015, 282(19):3722-3736.