Methylation and Expression of Nonclustered Protocadherins Encoding Genes and Risk of Precancerous Gastric Lesions in a High-Risk Population.

Nonclustered protocadherins (PCDH) family is a group of cell-cell adhesion molecules. We have found differentially methylated genes in the nonclustered PCDHs family associated with () infection in prior genome-wide methylation analysis. To further investigate the methylation and expression of nonclustered PCDHs encoding genes in -related gastric carcinogenesis process, four candidate genes including and were selected, which were reported to be tumor suppressors for digestive cancers. A total of 747 participants with a spectrum of gastric lesions were enrolled from a high-risk population of gastric cancer. Promoter methylation levels of four genes were significantly higher in positive subjects than the negative group (all < 0.001). Elevated methylation levels of and were observed with the increasing severity of gastric lesions (both < 0.001). In the protein expression analysis, PCDH17 expression was inversely associated with gastric lesions; the OR [95% confidence interval (CI)] was 0.49 (0.26-0.95) for chronic atrophic gastritis (CAG), 0.31 (0.15-0.63) for intestinal metaplasia, and 0.38 (0.19-0.75) for indefinite dysplasia and dysplasia, compared with superficial gastritis. In addition, PCDH10 expression was significantly lower in CAG (OR, 0.40; 95% CI, 0.24-0.68). The inverse association between methylation and protein expression of and 7 was further supported when we explored the methylation and mRNA expression in The Cancer Genome Atlas database (all < 0.001). Our study found elevated promoter methylation and decreased expression of and in advanced gastric lesions, suggesting that elevated and methylation may be an early event in gastric carcinogenesis. .