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

Abstract

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 Helicobacter pylori (H. pylori) infection in prior genome-wide methylation analysis. To further investigate the methylation and expression of nonclustered PCDHs encoding genes in H. pylori--related gastric carcinogenesis process, four candidate genes including PCDH7, PCDH10, PCDH17, and PCDH20 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 H. pylori-positive subjects than the negative group (all P < 0.001). Elevated methylation levels of PCDH10 and PCDH17 were observed with the increasing severity of gastric lesions (both P trend < 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 PCDH10 and PCDH17 was further supported when we explored the methylation and mRNA expression in The Cancer Genome Atlas database (all P < 0.001). Our study found elevated promoter methylation and decreased expression of PCDH10 and PCDH17 in advanced gastric lesions, suggesting that elevated PCDH10 and PCDH17 methylation may be an early event in gastric carcinogenesis. Cancer Prev Res; 11(11); 717-26. ©2018 AACR.

• Authors: Si Wu, Yang Zhang, Lian Zhang, Jun-Ling Ma, Tong Zhou, Zhe-Xuan Li, Wei-Dong Liu, Wen-Qing Li, Wei-Cheng You, Kai-Feng Pan
• Journal: Cancer prevention research (Philadelphia, Pa.) (Cancer Prev Res (Phila)) Vol. 11 Issue 11 Pg. 717-726 (11 2018) ISSN: 1940-6215 [Electronic] United States
• PMID: 30213786 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2018 American Association for Cancer Research.

Chemical References

• Cadherins
• PCDH10 protein, human
• PCDH17 protein, human
• Protocadherins

Topics

• Biopsy
• Cadherins (genetics, metabolism)
• Carcinogenesis (genetics)
• DNA Methylation
• Datasets as Topic
• Female
• Gastric Mucosa (diagnostic imaging, microbiology, pathology)
• Gastroscopy
• Helicobacter Infections (diagnosis, genetics, microbiology, pathology)
• Helicobacter pylori (isolation & purification)
• Humans
• Male
• Metaplasia (diagnosis, genetics, microbiology, pathology)
• Middle Aged
• Precancerous Conditions (diagnosis, genetics, microbiology, pathology)
• Promoter Regions, Genetic (genetics)
• Protocadherins
• Severity of Illness Index
• Stomach Neoplasms (genetics, pathology, prevention & control)