组织TMEFF2基因甲基化状态与子宫内膜癌和子宫内膜增生的关系  

Association of methylation status of TMEFF2 gene with endometrial cancer and hyperplastic endometrial lesions

作　　者：曾凡清[1] 殷娟[1] 胡静 郑颖[1] ZENG Fanqing;YIN Juan;HU Jing;ZHENG Ying(Department of Obstetrics and Gynecology,Chongqing Ninth People's Hospital,Chongqing 400799,China)

机构地区：[1]重庆市第九人民医院妇产科,重庆400799

出　　处：《检验医学与临床》2024年第17期2497-2501,2507,共6页Laboratory Medicine and Clinic

基　　金：重庆市科卫联合医学科研项目面上项目(2020MSXM019)。

摘　　要：目的分析含表皮样生长因子和卵泡抑素结构域的跨膜蛋白2(TMEFF2)基因甲基化状态与子宫内膜癌(EC)和子宫内膜增生的关系。方法选取2017年3月至2021年8月在该院妇产科住院的172例汉族女性为研究对象,包括91例EC患者(EC组)、36例子宫内膜增生患者(增生组)和45例子宫内膜正常女性(对照组)。采用实时定量焦磷酸测序检测TMEFF2基因3个CpG位点甲基化水平。根据甲基化指数(MI),将91例EC患者分为未甲基化组(MI<10%)、中低度甲基化组(MI为10%~30%)和高度甲基化组(MI>30%)。比较对照组、增生组、EC组临床资料,比较不同甲基化水平组各项临床和病理学特征。采用随机森林分类算法,根据变量在诊断中的重要性绘制出示意图,并对其进行排序,筛选鉴别诊断指标。采用受试者工作特征(ROC)曲线分析TMEFF2基因CpG1位点甲基化水平对EC、增生子宫内膜及正常子宫内膜的鉴别诊断价值。结果EC组、对照组、增生组TMEFF2基因MI分别为24.53(9.20,65.78)、4.58(0.49,15.76)、13.67(2.95,28.76),EC组MI明显高于对照组和增生组,且增生组MI明显高于对照组,差异均有统计学意义(P<0.05)。未甲基化组、中低度甲基化组、高甲基化组的EC肿瘤(pT)分期、淋巴结转移状态(pN)分期、年龄分布情况比较,差异均有统计学意义(P<0.05)。根据随机森林分类法,TMEFF2基因CpG1位点甲基化状态是仅次于体质量指数的重要诊断指标。ROC曲线分析结果显示,TMEFF2基因CpG1位点甲基化水平鉴别子宫内膜增生与正常子宫内膜、EC与子宫内膜增生的曲线下面积分别为0.700(95%CI:0.586~0.813,P<0.05)和0.933(95%CI:0.891~0.976,P<0.05)。结论TMEFF2基因CpG1位点甲基化异常与子宫内膜增生形成及增生组织进一步癌变密切相关,可作为潜在的预测因子。Objective To analyze the relationship between the methylation status of transmembrane protein with epidermal growth factor-like and two follistatin-like domains gene(TMEFF2)gene and endometrial carcinoma(EC),endometrial hyperplasia.Methods A total of 172 Han women hospitalized in the Department of Obstetrics and Gynecology of Chongqing Ninth People's Hospital from March 2017 to August 2021 were selected as the research objects,including 91 patients with EC(EC group),36 patients with endometrial hyperplasia(hyperplasia group)and 45 women with normal endometrium(control group).Quantitative pyrosequencing was used to detect three CpG loci of TMEFF2 gene.According to the methylation index(MI),91 EC patients were divided into unmethylated group(MI<10%),moderate-low methylation group(MI 10%-30%)and high methylation group(MI>30%).The clinical data of control group,hyperplasia group and EC group were compared,and the clinical data of different methylation level groups were compared.Using the random forest classification algorithm,draw a schematic diagram based on the importance of variables in diagnosis,and rank them to screen for differential diagnostic indicators.The area under the receiver operating characteristic(ROC)curve was used to analyze the value of TMEFF2 gene CpG1 methylation level in the differential diagnosis of EC,proliferative endometrium and normal endometrium.Results The MI of TMEFF2 gene in the EC group,control group,hyperplasia group were 24.53(9.20,65.78),4.58(0.49,15.76)and 13.67(2.95,28.76),the MI in EC group was significantly higher than those in control group and hyperplasia group,and the MI in hyperplasia group was significantly higher than that in control group,the differences were statistically significant(P<0.05).There were statistically significant differences on EC tumor(pT)stage,lymph node metastasis(pN)stage and age distribution among the unmethylated group,moderate-low methylation group and high methylation group(P<0.05).According to the random forest classification method,the methylatio

关 键 词：CpG位点 定量甲基化 含表皮样生长因子和卵泡抑素结构域的跨膜蛋白2 子宫内膜癌 子宫内膜增生 

分 类 号：R446.9[医药卫生—诊断学]