DNA Methylation as Surrogate Marker For Gastric Cancer

Abstract

Stomach cancer remains, stubbornly, highly prevalent in East Asia. Still, stomach cancer has few biomarkers by which it can be predicted. Helicobacter pylori infection, a known carcinogen of stomach cancer, usually goes undetected prior to cancer diagnosis, due to the poor mucosal environments that its related gastric atrophy causes. We propose, herein, an endoscopic-biopsy-based cancer-predicting DNA methylation marker. We semi-quantitatively examined the methylation-variable sites near the CpG-island margins by radioisotope-labeling methylation-specific polymerase chain reaction in association with H. pylori, which increases age-related over-methylation in CpG islands of gastric mucosa. These age-related methylation patterns of the transitional-CpG sites are proposed as useful surrogate markers for stomach cancer. It would be helpful for setting the optimal screening interval for high-risk subjects as well as for estimating the prognosis and the predictability for recurrence of early gastric cancer in patients having undergone endoscopic submucosal dissection. New screening-interval guidelines for gastric cancer should be suggested considering individual risk based on age, severity of atrophy, H. pylori status, and DNA methylation pattern.

Keywords: Biological markers; CpG Islands; DNA methylation; Helicobacter pylori; Stomach neoplasms.

Figure 1.

Methylation-variable CpG sites around transcriptional start sites. (A) Schematics displaying locations of transitional-CpG sites in housekeeping genes and stomach-specific genes. The transitional-CpG sites are located between the highly methylated retro-elements (closed box) and the weakly methylated genes (open box). (B) Comparison of methylation properties between CpG-island margins and CpG-island centers in housekeeping genes containing CpG islands.