Application of fecal DNA methylation biomarkers detection in gastric cancer screening

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.