Guo P, Zhou X J, Xu L, Chen H, Zhao L, Sun M H, Hu H
The First Affiliated Hospital of Soochow University,Suzhou 215006, China.
Zhonghua Yi Xue Za Zhi. 2021 Mar 23;101(11):808-812. doi: 10.3760/cma.j.cn112137-20200916-02659.
Explore the feasibility of fecal gene methylation for screening gastric cancer and its relationship with clinical characteristics of gastric cancer patients. 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 (=52)and test sets (=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. 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%). 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.
探讨粪便基因甲基化用于胃癌筛查的可行性及其与胃癌患者临床特征的关系。收集2018年8月至2019年12月苏州大学附属第一医院普外科或消化内科患者的156份粪便样本，记录胃癌患者的详细临床信息。所有患者及正常对照分为训练集（=52）和测试集（=104）两组。提取粪便DNA检测甲基化（SDC2、SFRP2、RASSF2和TERT）。同时，采用免疫分析法检测粪便样本中的血红蛋白。建立逻辑回归模型，通过各粪便DNA生物标志物的Ct值分析单个粪便DNA生物标志物检测胃癌的敏感性和特异性；基于赤池信息准则（AIC），构建各生物标志物及其组合的胃癌早期筛查模型，并在测试集中评估模型性能。各粪便生物标志物的准确性及其排序为：SDC2（71.2%）>TERT（67.3%）=RASSF2（67.3%）>Hb（63.5%）>SFRP2（61.5%）。通过逐步回归分析，由SDC2和TERT甲基化组成的组合，粪便潜血检测在胃癌筛查中表现良好。该组合在训练集和测试集中对胃癌的敏感性为66.7%，特异性为78.9%。在不同分期和部位的胃癌样本中，该标志物组合在Ⅰ期胃癌（78.6%）和胃体癌（75.0%）中敏感性最高。SDC2、SFRP2、TERT、RASSF2的甲基化在胃癌筛查中具有较高的准确率，是潜在的胃癌粪便生物标志物。
