Methylation Of The RUNX3 Gene Promoter Effect On Its Protein Expression And The Clinicopathological Features In Gastric Adenocarcinoma

Objective: To evaluate the aberrant methylation of the RUNX3 promoter effect on its protein expression and the correlation with the clinicopathological features of gastric adenocarcinomas. And explore a new therapentic target aim to the RUNX3 gene methylation.Methods: The clinical data and tumor tissue specimens of 52 cases with gastric adenocarcinoma were collected. And SP IHC method was used to detect the RUNX3 protein expression. And the RUNX3 promoter methylation was detected by MS-PCR. To analysis the correlations between the RUNX3 expression and the clinicaopathological features of these gastric adenocarcinomas.Results: 1. The ratio of RUNX3 protein expression were 32.7% (17/52) in gastric adenocarcinoma and 57.7% (30/52) in peri-adenocarcinoma tissue and 100% (52/52) in normal gastric mucosa respectively with a significant difference(P<0.05). The ratio of RUNX3 protein expression in poor or non differentiated tissue group was 23.8% (10/42), which was significantly lower than that 70% (7/10) in well or moderate differentiated group (P<0.05). The ratio of RUNX3 protein expression in cases with regional lymph node metastasis was 20% (6/30), which was significantly lower than that 50% (11/22) in node-negative group (P<0.05). The ratio of RUNX3 expression inâ…¢~â…£ cases was 16% (4/25), which was significantly lower than that 48.1% (13/27) inâ… ~â…¡cases(p<0.05). 2. The aberrant methylation of RUNX3 promoter were 73.1% (38/52) in gastric adenocarcinoma and 48.1% (25/52) in peri-adenocarcinoma tissue and 11.5% (6/52) in normal gastric mucosa respectively with a significant difference (p<0.05). The aberrant methylation of RUNX3 promoter was 81% (34/42) in poor or non differentiated gastric adenocarcinoma group, which was higher than that 40% (4/10) in well or moderate differentialed (p<0.05). The aberrant methylation of RUNX3 promoter in regional lymph node metastasis cases was 86.7% (26/30), which was significantly higher than that 54.5% (11/22) in lymph node-negative cases group(p<0.05). The aberrant methylation of RUNX3 promoter inâ…¢~â…£cases was 92.0% (23/25), which was significantly higher than that 55.6% (15/27) inâ… ~â…¡cases group(p<0.05). 3. There was a significant correlation between the aberrant methylation of RUNX3 promoter and its down-regulation through Spearman correlation analysis.Conclusions: 1. The down-regulation of RUNX3 protein was found in gastric adenocarcinoma, which was related decreased with the lower degree of differentiated and the regional lymph node metastasis and the increase of stage in gastric adenocarcinoma. 2. The methylaiton of RUNX3 promoter was the main mechanism for down-regulation of the RUNX3 gene in gastric adenocarcinoma. 3. The RUNX3 gene may become a new therapeantic target of molecular and biology of gastric adenocarcinoma.