Expression And Significance Of FOXO4in Carcinogenesis Of Gastric Mucosa And Its Relationship With H. Pylori Infection

Objective:Gastric cancer is a common malignant tumor of the human. It may involve excessive proliferation, blocked apoptosis, disordered differentiation of gastric epithelial cells. Studies have shown that FOXO factors may play a tumor suppressor role in a variety of cancer. FOXO4is a member of the FOXO subfamily. It is becoming more and more attention in cancer pathogenesis research because of its involving in regulation of cell proliferation, apoptosis and differentiation process. But so far the exact role of FOXO4in gastric cancer has not yet been elucidated. Helicobacter pylori (Hp) is an important risk factor for gastric cancer. Its function and the correlation between Hp infection and FOXO4in carcinogenesis of gastric mucosa are updately unknown. This study is to investigate the expressions and the clinical significance of FOXO4in human carcinogenesis of gastric mucosa and its relationship with Hp infection.Methods:The expressions of FOXO4were detected by immunohistochemistry assay in human tissues, including16cases of normal gastric mucosa (the NGM group),26cases of intestinal metaplasia (the IM group),36cases of atypical hyperplasia (the AH group) and60cases of gastric adenocarcinoma (the GAC group). And further research the relationship between the FOXO4expression and clinicopathological parameters of gastric cancer. Hp infection was detected by boric acid methylene blue staining. And further research the relationship between Hp infection and FOXO4expression. Data analysis are applicated by SPSS17.0statistical software. The analysis of the expres-sion of FOXO4in gastric mucosal lesions at all levels, the relationship that between the expression of FOXO4and gastritis cancer’clinical pathological parameters and the correlation between FOXO4’expression with Hp infection are performed using the χ2test.Results:1. Expressions of FOXO4in gastric mucosa lesions at all levelsThe positive rates of FOXO4in the NGM group, the IM group, the AH group and the GAC group were100%,84.6%,69.4%and40.0%respectively, showing a decreasing trend. The level of FOXO4expression in the GAC group was significantly lower than that in the NGM group (P<0.01). There was no statistically significant difference between NGM group and IM group, so was the IM group with the AH group.(P>0.05). There were significant differences between the NGM group and the AH group, the NGM group and the GAC group, the IM group and the GAC group, the AH group and the GAC group (P<0.05).2. Relationship between expressions of FOXO4and clinicopathological parameters of gastric carcinoma patientsThe expression rates of FOXO4in gastric cancer tissues had no significant correlations with sex, age and tumor size (P>0.05), but significantly been associated with the cell differentiation, lymph node metastases, TNM stage and the depth of invasion (P<0.05). The expression rate of FOXO4in poorly differentiated gastric carcinoma was obviously lower than that in medium and well differentiated gastric carcinoma (P=0.005). Similarly, the expression level of FOXO4in lymph node metastasis group was significantly lower than that in no lymph node metastasis group (P=0.007). Again, its expression level in the â…¢ and â…£ period group of TNM staging was significantly lower than that in the â…  and â…¡ period group (P=0.004). Tumor invasion not penetrate muscle group was significantly higher than the infiltration the serosa/plasma layer film outside group (P=0.004). 3. Relationship between the expression of FOXO4and Hp infectionThere were no significant correlation between the expression of FOXO4and Hp infection rates in intestinal metaplasia and gastric adenocarcinoma lesions (P>0.05). On the contrary, there was a negative relation between the expression of FOXO4and Hp infection rates in aqtypical hyperplasia of gastric mucosa (P<0.01, Cramer’s V coefficient=0.738).Conclusions:(1) Normal gastric mucosaâ†'chronic atrophic gastritis with intestinal metaplasiaâ†'chronic atrophic gastritis with atypical hyperplasiaâ†'gastritis cancer, the expression level of FOXO4is decreased, especially in the gastric cancer phase significantly. It is prompted the FOXO4transcription factors may play a tumor suppressor role in the development of gastric cancer. Its anti-tumor mechanism may include cell cycle regulation, regulation of apoptosis. It is inferred that FOXO transcription factor may be a negative regulator of cell proliferation process, and also is an promoting factor in apoptosis process.(2) The expression level of FOXO4has correlation with the degree of tumor differentiation, lymph node metastasis, depth of invasion, TNM staging (P<0.05), suggesting that FOXO4may be involved in the differentiation and metastasis of gastric cancer cells.(3) There is a positive relation between the expression of FOXO4and Hp infection rates in aqtypical hyperplasia of gastric mucosa, indicated that the expression of FOXO4may be closely related with some apoptosis-promoting factors of Hp infection. This may be one of the important mechanism of Hp infection inducing apoptosis in gastric epithelial cells.