Abstract
Gastric cancer (GC) is one of the most common and deadly cancers worldwide. Early detection offers the best chance for curative treatment and reducing its mortality. However, the optimal population-based early screening for GC remains unmet. Aberrant DNA methylation occurs in the early stage of GC, exhibiting cancer-specific genetic and epigenetic changes, and can be detected in the media such as blood, gastric juice, and feces, constituting a valuable biomarker for cancer early detection. Furthermore, DNA methylation is a stable epigenetic alteration, and many innovative methods have been developed to quantify it rapidly and accurately. Nonetheless, large-scale clinical validation of DNA methylation serving as tumor biomarkers is still lacking, precluding their implementation in clinical practice. In conclusion, after a critical analysis of the recent existing literature, we summarized the evolving roles of DNA methylation during GC occurrence, expounded the newly discovered noninvasive DNA methylation biomarkers for early detection of GC, and discussed its challenges and prospects in clinical applications.