粪便DNA甲基化标志物检测在胃癌筛查中的应用  

Application of fecal DNA methylation biomarkers detection in gastric cancer screening

作　　者：郭鹏 周晓俊[1] 徐露[1] 陈鸿[1] 赵林 孙明浩 胡浩[1] Guo Peng;Zhou Xiaojun;Xu Lu;Chen Hong;Zhao Lin;Sun Minghao;Hu Hao(The First Affiliated Hospital of Soochow University,Suzhou 215006,China)

机构地区：[1]苏州大学附属第一医院普通外科,苏州215006

出　　处：《中华医学杂志》2021年第11期808-812,共5页National Medical Journal of China

摘　　要：目的探讨粪便DNA甲基化标志物检测用于胃癌筛查的可行性以及与胃癌患者临床特征的关系。方法前瞻性收集2018年8月至2019年12月在苏州大学附属第一医院普通外科及消化内科就诊的胃癌患者及胃镜检查阴性者的粪便样本共156份,同时收集胃癌患者术前及术后的临床资料。按照1∶2的比例将这些样本随机分成训练集(n=52)和测试集(n=104)。提取粪便中的DNA,然后检测Syndecan-2黏结蛋白聚糖2基因(SDC2)、分泌性卷曲蛋白2基因(SFRP2)、Ras相关区域家族2基因(RASSF2)、端粒酶逆转录酶基因(TERT)甲基化水平,同时用免疫胶体金法检测粪便中血红蛋白(Hb)含量。使用单项粪便DNA标志物的Ct(Cycle threshold荧光信号到达设定阈值时所经历的循环次数)值建立logistic回归模型,分析单个标志物检测胃癌的灵敏度和特异度;基于Akaike信息准则(AIC),使用多因素逻辑回归及逐步回归分析筛选最优的标志物组合,并在测试集中评价胃癌早期筛查标志物组合筛查/检测胃癌的效果。结果各标志物区分胃癌和阴性对照的准确度排序为:SDC2甲基化(71.2%)>TERT甲基化(67.3%)=RASSF2甲基化(67.3%)>Hb(63.5%)>SFRP2甲基化(61.5%)。通过逐步回归分析,在训练集中筛选出一个由SDC2甲基化、TERT甲基化和Hb组成的粪便生物标志物组合,在训练集及测试集中检测胃癌的总灵敏度为66.7%,总特异度为78.9%。在不同分期以及不同部位胃癌样本中,该标志物组合对Ⅰ期胃癌及胃体部胃癌的灵敏度(分别为78.6%、75.0%)最高。结论粪便中SDC2、SFRP2、TERT、RASSF2基因甲基化标志物在胃癌筛查中具有一定的灵敏度和较高的特异度,是胃癌早期筛查中的潜在粪便生物标志物。Objective Explore the feasibility of fecal gene methylation for screening gastric cancer and its relationship with clinical characteristics of gastric cancer patients.Methods One hundred and fifty-six stool samples of patients in general surgery or digestive department of the First Affiliated Hospital of Soochow University from August 2018 to December 2019 were collected,detailed clinical information of gastric cancer patients were recorded.All patients and normal controls were divided into two sets including train sets(n=52)and test sets(n=104).Stool DNA was extracted for detection of methylation(SDC2,SFRP2,RASSF2 and TERT).Meanwhile,hemoglobin in stool samples were detected by immunoassays.A logistic regression model was built to analyze the sensitivity and specificity of single fecal DNA biomarker in detecting gastric cancer by Ct values of each stool-based DNA biomarker;Based on Akaike information criterion(AIC),the gastric cancer early screening model was constructed with each biomarker and the combinations,and evaluate the performance of the model in the test sets.Results The accuracy of each stool biomarkers and their ranks were showed as SDC2(71.2%)>TERT(67.3%)=RASSF2(67.3%)>Hb(63.5%)>SFRP2(61.5%).By stepwise regression analysis,a combination composed of the methylation of SDC2 and TERT,fecal occult blood testing was well-behaved in the screening of gastric cancer.This combination showed a sensitivity of 66.7%for gastric cancer in train sets and test sets at the specificity of 78.9%.In different stages and parts of gastric cancer samples,the combination of this marker has the highest sensitivity in stage I gastric cancer(78.6%)and gastric body cancer(75.0%).Conclusion The methylation of SDC2,SFRP2,TERT,RASSF2 has higher accuracy rate in the screening of gastric cancer,which is a potential fecal biomarker of gastric cancer.

关 键 词：胃肿瘤 早期筛查 粪便生物标志物 DNA甲基化 

分 类 号：R735.2[医药卫生—肿瘤]