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Updated: May 9, 2026
Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Detection and Recurrence Risk Stratification of Gastric Cancer Through DNA Methylation Profiling of Blood
Jing Guo1, Shun Zhang2, Shuang Zhou3
1Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Purpose:
The purpose of this study was to develop a blood-based DNA methylation assay for noninvasive detection of gastric cancer (GC) across all stages, including early and premalignant lesions, and to evaluate whether preoperative GasAiQ positivity is associated with postoperative recurrence risk in patients with resectable GC.
Materials And Methods:
We used reduced representation bisulfite sequencing to profile DNA methylation patterns and identify tumor-specific differentially methylated regions between patients with GC and controls. The 24 most discriminatory differentially methylated regions were validated in an independent set of tissues and plasma and then incorporated into a real-time methylation-specific PCR assay, GasAiQ. GasAiQ was evaluated in 1372 individuals, including GC patients and those with gastritis, atrophy, intestinal metaplasia, or intraepithelial neoplasia, across 3 cohorts: training (n = 518), validation (n = 519), and independent test (n = 335). Its association with recurrence risk was also assessed in 203 GC patients with resectable tumors for whom follow-up data were available after surgical resection.
Results:
GasAiQ demonstrated high diagnostic accuracy across all cohorts. In the training cohort, an area under the curve (AUC) of 0.904 was achieved, with 83.8% sensitivity, 82.6% specificity, and 83.2% accuracy. The performance remained robust in the validation (AUC, 0.878; 83.9% sensitivity, 81.9% specificity, and 81.5% accuracy) and independent test (AUC, 0.891; 83.5% sensitivity, 86.3% specificity, and 85.3% accuracy) cohorts. The detection rates for early-stage GC (stage I) ranged from 70.2% to 75.0%, and GasAiQ identified 57.6% high-grade intraepithelial neoplasia. Notably, in a multivariate Cox regression model adjusting for key clinicopathological factors, preoperative GasAiQ positivity remained significantly associated with recurrence risk (hazard ratio, 7.5; 95% CI, 1.0-55.2; P = .047), supporting its potential prognostic value.
Conclusions:
GasAiQ is a noninvasive methylation assay that accurately detects GC, including early and premalignant stages, and predicts recurrence risk, offering significant potential for advanced screening, early diagnosis, and postoperative management.
