良恶性肺疾病组织前列腺素E受体4基因甲基化水平变化及其诊断价值研究  

A Study on the Diagnostic Utility of the Prostaglandin E Receptor 4 Gene’sMethylation Alterations in Tissues Associated with Benign and Malignant Lung Diseases

作　　者：朱玲 任德旺 马润阳 窦学军[2] 梁国威[1] ZHU Ling;REN Dewang;MA Runyang;DOU Xuejun;LIANG Guowei(Department of Clinical Laboratory,Aerospace Central Hospital,Beijing 100049,China;Department of Thoracic Surgery,Aerospace Central Hospital,Beijing 100049,China)

机构地区：[1]航天中心医院检验科,北京100049 [2]航天中心医院胸外科,北京100049

出　　处：《标记免疫分析与临床》2023年第5期748-752,757,共6页Labeled Immunoassays and Clinical Medicine

基　　金：北京市重点专科建设项目。

摘　　要：目的探讨良恶性肺疾病组织中前列腺素E受体4(PTGER4)基因甲基化水平及其诊断肺恶性肿瘤价值。方法收集我院胸外科患者术后冰冻组织标本174例,根据病理结果分为肺腺癌组60例,鳞癌组38例,错构瘤组17例、良性疾病组31例和肺正常组织组28例,收集临床基础资料,分别提取组织DNA。PTGER4基因甲基化水平检测采用甲基化敏感限制性内切酶-荧光定量PCR方法,根据PTGER4基因与内参ACTB基因的循环阈值差异(ΔCt值)判断甲基化程度。结果肺腺癌组、肺鳞癌组、良性疾病组、错构瘤组和肺正常组织组ΔCt值的中位数(四分位数)[M(P 25,P 75)]分别为0.21(-0.67,1.20)、1.75(-0.04,4.10)、6.02(4.36,7.57)、7.17(5.72,8.78)和4.61(3.65,5.10),根据ΔCt比较,肺腺癌和肺鳞癌组PTGER4甲基化水平显著高于良性疾病组、错构瘤组和肺正常组织组(P<0.05)。肺腺癌甲基化水平显著高于肺鳞癌(P=0.044)。ROC曲线分析显示,PTGER4基因甲基化诊断总的肺癌的曲线下面积(AUC)、灵敏度和特异性分别为0.923、79.6%和98.7%,诊断肺腺癌为0.984、90.0%和98.7%,鳞癌为0.828、65.8%和96.1%,腺癌AUC显著高于鳞癌(P<0.05)。肺癌患者PTGER4基因甲基化水平与年龄、性别、吸烟、肿瘤标志物(CEA、NSE、CYFRA21-1、SCC)和肿瘤分期无显著性相关(P>0.05)。结论肺恶性肿瘤组织中PTGER4基因甲基化呈现特异性升高;PTGER4基因甲基化对肺腺癌的诊断效能更高。Objective To investigate the methylation level of the prostaglandin E receptor 4(PTGER4)gene in benign and malignant lung diseases and its diagnostic value for lung cancer.Methods Following thoracic surgery,174 cases of postoperative frozen tissue samples from patients were collected for the study.Based on pathological findings,these patients were divided into 60 cases of lung adenocarcinoma,38 cases of squamous cell carcinoma,17 cases of hamartoma,31 cases of benign disease,and 28 cases of normal lung tissue.Basic clinical information was gathered,and tissue DNA was extracted for all patients.The methylation level of PTGER4 gene was detected by the methylation-sensitive restriction endonuclease-fluorescence quantitative PCR method,and the methylation level was determined based on the cycling threshold difference(ΔCt value)between the PTGER4 gene and the internal reference ACTB gene.Results Adenocarcinoma,squamous cell carcinoma,benign illness,hamartoma,and normal tissue groups had median(P 25,P 75)values ofΔCt of 0.21(-0.67,1.20),1.75(-0.04,4.10),6.02(4.36,7.57),7.17(5.72,8.78),and 4.61(3.65,5.10),respectively.In comparison toΔCt value,PTGER4 methylation levels in the lung adenocarcinoma and squamous cell carcinoma groups were markedly greater than those in the benign disease,hamartoma,and normal lung tissue groups(P<0.05).The methylation level of lung adenocarcinoma was significantly higher than that of lung squamous carcinoma(P=0.044).ROC curve analysis showed that the area under the curve(AUC),sensitivity,and specificity of PTGER4 gene methylation in the diagnosis of total lung cancer were 0.923,79.6%,and 98.7%,respectively,while those in the diagnosis of lung adenocarcinoma were 0.984,90.0%,and 98.7%,and those in squamous cell carcinoma were 0.828,65.8%,and 96.1%,respectively.AUC of adenocarcinoma was significantly higher than that of squamous cell carcinoma(P<0.05).The methylation level of the PTGER4 gene in lung cancer patients was not significantly correlated with age,sex,smoking,tumor markers(CEA,NSE,

关 键 词：PTGER4 甲基化 腺癌 鳞癌 组织 

分 类 号：Q343.1[生物学—遗传学]