IRF4、ELMO1、CLIP4和MSC启动子甲基化水平在胃癌早期筛查中的应用价值分析  

Application value of IRF4,ELMO1 and CLIP4 promoter methylation levels in early screening of gastric cancer

作　　者：谭玉娥[1] 刘鑫[2] TAN Yu’e;LIU Xin(Gastro-endoscopic Room,Affiliated Hospital of Yan’an University,Shaanxi,Yan’an 716000, China)

机构地区：[1]延安大学附属医院胃镜室,陕西省延安市716000 [2]延安大学附属医院消化内科,陕西省延安市716000

出　　处：《河北医药》2021年第2期182-186,共5页Hebei Medical Journal

基　　金：延安市科技创新平台项目(编号:2016CXTD—05)。

摘　　要：目的研究开发一种分子工具,通过内镜活检技术预测胃癌风险。方法收集2014至2018年共282例高风险胃癌患者,在其内镜样本中发现并验证了1个DNA甲基化生物标物组合,并在癌症基因组图谱项目(“TCGA”)的298个样本中进行了验证。采用全基因组、表观基因组和基因特异性DNA甲基化分析,确定一个连续的生物标志物组合,该组合结合了总体DNA甲基化指数(global DNA methylation index,GDMI)和IRF4、ELMO1、CLIP4和MSC启动子DNA甲基化水平。结果比较未发生化生的胃炎患者(平均值=5.69,95%CI,4.88~6.45)、发生化生的胃炎患者(平均值=4.68,95%CI,3.67~5.73)和胃癌患者(平均值=3.36,95%CI,2.81~3.93)(P<0.0001),发现胃癌的GDMI与组织学进展呈负相关。IRF4(P<0.01)、ELMO1(P<0.01)、CLIP4(P<0.01)和MSC(P<0.01)启动子甲基化与从无化生的胃炎到有化生的胃炎再到胃癌的严重程度增加相关。结论IRF4、ELMO1、CLIP4和MSC启动子甲基化结合GDMI>4是内镜活检中胃癌风险分层的有效分子工具。Objective To investigate a molecular tool to predict the risk of gastric cancer(GC)through the endoscopic biopsy.Methods A total of 282 patients with high risk gastric cancer who were admitted and treated in our hospital from 2014 to 2018 were enrolled in the study.A combination of DNA methylated biomarker panel was found and verified in 298 specimens of the cancer genome mapping project(“TCGA”).A sequential biomarker panel was identified by the analysis of genome wide,epigenome and gene specific DNA methylation,which combined with global DNA methylation index(GDMI),and the DNA methylation levels of the promoters of IRF4,ELMO1,CLIP4 and MSC.Results The GDMI of gastric carcinoma has a negative correlation with the histological progress of gastric cancer,as compared with that in patients with gastritis without metaplasia(mean value=5.69,95%CI,4.88~6.45),the gastritis patients with metaplasia(mean value=4.68,95%CI,3.67~5.73)and the gastric cancer patients(mean value=3.36,95%CI,2.81~3.93)(P<0.01).The promoter methylation of IRF4,ELMO1,CLIP4 and MSC were closely correlated with the increase of severity from gastritis without metaplasia to gastritis with metaplasia,then to gastric cancer.Conclusion The combination of the promoter methylation of IRF4,ELMO1,CLIP4 and MSC and the GDMI>4 is effective molecular tool for gastric cancer risk stratification in endoscopic biopsy.

关 键 词：内镜活检 DNA甲基化 甲基化指数 胃癌早筛 

分 类 号：R735.2[医药卫生—肿瘤]