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 () 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 inpositive 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 and7 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. .

Genome wide methylation profiling of selected matched soft tissue sarcomas identifies methylation changes in metastatic and recurrent disease

“…In a single study in breast cancer cells, PTPRN2 was shown to regulate actin dynamics, enhancing metastatic migration 40 and based on this, we can hypothesise that PTPRN2 is also likely to act as a key regulator in the metastatic cascade of leiomyosarcomas but functional analyses are required to confirm this. Methylation modifications in other of the identified genes (PCDH20, CDEB, KCNQ1, MCF2L, LTB4R and PRODH) [41][42][43][44] have been described in carcinomas but their role in the pathogenesis of leiomyosarcoma progression has not been reported (apart from PCDH2 and PRODH 45 ), and should be further explored. Finally, we also looked into overlapping genes in our list with other similar studies of primary LMSs.…”