Expression And Clinical Significance Of DNMT1and PDCD4in Gastric Carcinoma And Precancerous Lesion

Objective:To study the expression of DNA methylation transfer enzyme1(DNMT1) and programmed cell death factor4(PDCD4) protein in gastric carcinoma and precancerous lesions, and to explore the relationship between DNMT1and PDCD4and analyze their connection to clinicopathological findings, so that we can development a new idea for the clinical diagnosis and treatment of gastric cancer.Methods:Immunohistochemical SP method was used to the detected the expression of DNMT1and PDCD4in the samples of gastric adenocarcinoma (GAC, n=62), intraepithelial neoplasia (IN, n=36), intestinal metaplasia(IM, n=27) and normal gastricmucosa (NGM, n=20), and their correlations with the age, pathological type, lymph node metastasis, TNM stage and other clinicopathological parameters were analyzed.Results:1. The positive rates of DNMT1in gastric adenocarcinoma, intestinal metaplasia, intestinal metaplasia and normal gastric mucosa were respectively77.4%,58.3%,44.4%and15.0%. Significant difference was found in the expression of DNMT1between the first three groups and the last group (P<0.05)2. The positive rates of PDCD4in gastric adenocarcinoma, intestinal metaplasia, intestinal metaplasia and normal gastric mucosa were respectively30.6%,50.0%,70.4%and100.0%. The difference between the first three groups and the last group. Had statistical significance (P<0.05)3. The relationship between DNMT1protein expression and clinicopathological parameters in gastric adenocarcinoma:overexpression of DNMT1were significantly associated with pathological differentiation of type(P<0.05), regardless of age, lymph node metastasis and TNM stage. The relationship between PDCD4protein expression and clinicopathological parameters in gastric adenocarcinoma:lowerxpression of PDCD4were significantly associated with pathological differentiation type, lymph node metastasis and TNM stage (P<0.05), regardless of age.4. Two protein expression in62cases of gastric cancer patients were positive in seven cases, two cases were negative, Spearman correlation analysis showed that there was a significant negative correlation between PDCD4and DNMT1expression in gastric cancer (r=-0.645, P<0.01).Conclusion:1. Overexpression of DNMT1protein and lowerexpression of PDCD4in gastric cancer tissues closely related with tumorigenesis.2. Because overexpression of DNMT1were significantly associated with pathological differentiation of type(P<0.05), regardless of age, lymph node metastasis and TNM stage and there was a relationship between PDCD4protein expression and pathological differentiation type, lymph node metastasis and TNM stage (P<0.05), regardless of age, we can speculate that the expression changes of DNMTl protein is an early event in gastric cancer and PDCD4may play an important role in promoting the development of gastric cancer.3. There was a negative correlation between DNMT1and PDCD4(P=0.000)in gastric carcinoma and DNMT1may participates in the inactivation of PDCD4expression through methylation mechanism.4. Joint detection of DNMT1and PDCD4protein expression status may contribute to early diagnosis of gastric cancer. Inhibition of DNMTl and restore normal expression of PDCD4may become a new target for the treatment of gastric cancer.