环状RNA circDYSF在不同类型冠心病患者外周血中的表达及临床价值探讨  

Expression analysis and clinical significance of circular RNA circDYSF in patients with different types of coronary artery disease

作　　者：赵静雯 于海奕[1] 张永珍[1] 高炜[1] ZHAO Jing-wen;YU Hai-yi;ZHANG Yong-zhen;GAO Wei(Department of Cardiology and Institute of Vascular Medicine,Peking University Third Hospital,Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides,Ministry of Health,Key Laboratory of Molecular Cardiovascular Science,Ministry of Education,Beijing Key Laboratory of Cardiovascular Receptors Research,Beijing 100191,China)

机构地区：[1]北京大学第三医院心内科,国家卫生健康委心血管分子生物学与调节肽重点实验室,分子心血管学教育部重点实验室,心血管受体研究北京市重点实验室,北京100191

出　　处：《中国介入心脏病学杂志》2022年第11期801-807,共7页Chinese Journal of Interventional Cardiology

基　　金：国家重点研发计划基金项目(2017YFC0908701)。

摘　　要：目的探讨环状RNA circDYSF在不同类型冠心病患者外周血中的表达水平及其临床价值。方法前瞻性研究入组2018年8月至2020年6月在北京大学第三医院就诊的不同类型冠心病患者,包括慢性冠状动脉综合征(CCS)、不稳定型心绞痛(UAP)和ST段抬高型心肌梗死(STEMI)各50例。以同期经临床及冠状动脉造影除外冠心病的患者43例为对照组。采用高通量测序检测circDYSF在不同类型冠心病患者外周血中的表达量。Pearson或Spearman分析评价circDYSF表达量与心肌损伤标志物及冠状动脉病变Gensini评分的相关性。对行血管内光学相干断层成像(OCT)的患者进行亚组分析,探索circDYSF在稳定斑块组及不稳定斑块组的表达差异。通过生物信息学分析circDYSF调控的靶基因并预测其可能参与的生物学过程。结果circDYSF在冠心病患者中的表达量(36.22±18.44)TPM高于对照组(24.63±15.38)TPM(P=0.008),其中STEMI组患者最高(40.65±25.62)TPM,其次为UAP组(31.40±14.81)TPM和CCS组(28.17±14.09)TPM,三组相比较,差异有统计学意义(P=0.031)。circDYSF表达量与冠心病患者心肌肌钙蛋白T(r=0.379,P<0.001)、肌酸激酶同工酶(r=0.362,P<0.001)以及N末端B型脑钠肽前体(r=0.166,P=0.012)正相关,与左心室射血分数负相关(r=–0.336,P<0.001)。circDYSF表达量与冠状动脉病变Gensini评分呈正相关(r=0.287,P<0.001)。亚组分析显示,circDYSF在不稳定斑块组中的表达水平高于稳定斑块组[48.62(39.02,74.68)TPM比29.32(20.89,45.65)TPM,P=0.043],其识别不稳定斑块的曲线下面积为0.77(95%CI 0.53~0.93,P=0.017),敏感度90.0%,特异度60.0%。circDYSF调控的下游基因显著富集于溶酶体途径和腺苷酸活化蛋白激酶信号通路等。结论circDYSF在不同类型冠心病中存在差异,STEMI时表达量更高;circDYSF与斑块不稳定有关,可能有助于不同类型冠心病的鉴别诊断。Objective To explore the expression level of circular RNA circDYSF in peripheral blood of patients with different types of coronary heart disease and its clinical significance.Methods Patients with different types of coronary artery disease admitted to Peking University Third Hospital from August 2018 to June 2020 were prospectively analyzed,including 50 patients with chronic coronary syndrome(CCS),50 patients with unstable angina pectoris(UAP)and 50 patients with ST-segment elevation myocardial infarction(STEMI).Forty-three patients with exclusion of CAD by clinical symptoms and coronary angiography during the same period were enrolled as the control group.High throughput sequencing was used to detect the expression level of circDYSF.Correlation analysis was performed to evaluate the relationship between circDYSF and clinical indicators such as myocardial injury markers and coronary lesion scores.A subgroup analysis of patients who underwent intravascular optical coherence tomography(OCT)were performed to explore the differences of circDYSF expression level in the stable and unstable plaque groups.Pathway enrichment analysis of target genes regulated by circDYSF was performed to predict the possible biological processes involved.Results The expression level of circDYSF in CAD patients(36.22±18.44)TPM was higher than that in the controls(24.63±15.38)TPM(P=0.008).Among the CAD,circDYSF was highest in STEMI(40.65±25.62)TPM,followed by UAP(31.40±14.81)TPM and CCS(28.17±14.09)TPM(P=0.031).CircDYSF was positively correlated with the peak value of troponin T(r=0.379,P<0.001),creatine kinase isoenzyme MB(r=0.362,P<0.001),and N-terminal brain natriuretic peptide precursor(r=0.166,P=0.012),and negatively correlated with left ventricular ejection fraction(r=-0.336,P<0.001).CircDYSF was positively correlated with Gensini score(r=0.287,P<0.001).In the subgroup analysis,the expression level of circDYSF in the unstable plaque group was higher than that in the stable plaque group[48.62(39.02,74.68)TPM vs.29.32(20.89,45.65)

关 键 词：冠心病 环状RNA 生物标志物 不稳定斑块 

分 类 号：R541[医药卫生—心血管疾病]