A great number of genes with promoter methylation have been observed in gastric cancer (GC), among which p16INK4A (p16), Mut L homologue 1 (MLH1), Epithelial-cadherin (E-cadherin), Runt-related transcription factor 3 (RUNX3), adenomatous polyposis coli (APC), O(6)-methylguanine-DNA methyltransferase (MGMT), Ras association domain family 1A (RASSF1A) and Death-associated protein kinase (DAPK) have been extensively studied.
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.
To investigate the expression of human telomerase reverse transcriptase gene (hTRT) in gastric cancer (GC) and its relevance with cell cycle regulators including P16INK4, cyclin and P53.
Cytotoxicity of 5-Aza-2'-deoxycytidine against gastric cancer involves DNA damage in an ATM-P53 dependent signaling pathway and demethylation of P16(INK4A).
The present study demonstrated for the first time that gastric cancer patients with p16INK4a methylation specifically benefit from 5-FU-based adjuvant chemotherapy.
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.
These results suggest that at least two types of promoter methylation status are involved in the development of the intestinal (p16(INK4a) promoter hypermethylation) and diffuse-scattered types (CDH1 and RAR-beta promoter hypermethylation) of gastric carcinoma.
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).
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.
p16(INK4a) and p14(ARF) genes are frequently inactivated by homozygous deletion and methylation of the 5'CpG islands in gastric cancer, which may play an important role in the carcinogenesis of gastric cancer.
For determination of association between DNA methylation pattern or histological type and CIMP status in gastric carcinoma, CpG islands in the promoters of hMLH1 and CDH1 genes, CpG islands overlapping exon 1 of MGMT and p16(INK4a) genes, and a non-CpG island in exon 1 of the RAR-beta gene were studied.
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).
Our results demonstrate that STAT3, but not STAT5, is involved in GC cell growth and cell cycle progression through regulation of gene expression, such as Bcl-2, p16(ink4a) and p21(waf1/cip1).