Relative expression of SNHG7 is upregulated in gastric cancer tissues and cells, and partially contributes to the development and progression of gastric cancer through regulation of p15 and p16 expressions.
However, there were no correlations of p16 promoter methylation with the TNM stage and Helicobacter pylori (HP) infection of GC (Tumor size: OR = 0.76, 95% CI: 0.14-4.07, P = 0.746; HP infection: OR = 1.31, 95% CI: 0.75-2.27, P = 0.342; respectively).
In addition, p16 methylation in chronic gastritis lesions significantly correlated with H. pylori infection; however, such correlation was not observed in GC specimens.
Evaluating LINE-1, TP53 and p16 jointly yielded a more pronounced negative association with gastric cancer (OR: 0.24; 95% CI: 0.09-0.66).Age was a significant effect modifier.
In nonneoplastic mucosa, p14, p16 and p73 methylation occurred in both EBV-associated (8/33, 6/34 and 3/38, respectively) and EBV-negative GC (6/23, 4/35, and 1/35). p73 methylation was observed in the mucosa without H. pylori infection in all 4 samples.
The frequencies of LOH in two microsatellite sites, D9s171 and D9s1604, in p16 genome were associated with development of gastric cancer and no significant correlation was demonstrated between the LOH frequency and the cell differentiated types of tumor cells or clinical stages.
Thus, a marked decrease of p16 expression, caused by the aberrant methylation of the p16 gene promoter, is closely associated with the development of EBVaGC.
The overexpression of p16 seems to be a common event in the development of both intestinal and diffuse type of gastric cancer and it is likely that it may be driven by features of the neoplastic state.
The positive rate of p16 protein expression in gastric carcinoma was significantly lower than that in normal gastric mucosa and dysplastic gastric mucosa (P < 0.05).
The relatively high frequency of hypermethylation on p16 and the strong correlation between the immunoreactivity and methylation patterns suggest that methylation is an important mechanism for p16 gene inactivation in GC.
Taken together, these results suggest a strong correlation between de novo methylation of a few specific CpG sites and transcriptional silencing of the p16 gene in gastric carcinoma.
Our preliminary results indicate alterations in the p15 gene were not important in gastric tumorigenesis, while infrequent homozygous deletions in the p16 gene play a limited role in tumour progression of intestinal-type GC.
However, defective mRNA transcription, sometimes by aberrant DNA methylation, might be one of the pathways of inactivation of the p16 gene that leads to the development of gastric carcinoma.