Study Of The Role Of Inflammatory Microenvironment Changes Induced By Helicobacter Pylori In Atrophic Gastritis And Gastric Cancer

Background and objective Chronic atrophic gastritis (CAG) is a popular digestive disease in China. CAG is the most common precancerous condition of stomach characterized by the loss of gastric glandular structures, which is usually accompanied by extensive intestinal metaplaia (IM) and atypical hyperplasia (AH). It is accepted that a long multistep accumulation process of polygenic mutations affected by multiple etiologies leads to CAG With in-depth study on CAG, it is generally acknowledged that the evolution of CAG initiates from normal mucosa to inflammation, atrophy, intestinal metaplaia, dysplasia and, finally, leads to the development of gastric cancer (GC). Therefore, an early and correct diagnosis is essential for treatment and improving prognosis of CAG, which is also an important initiative for prevention and early detection of GC. During the process of chronic atrophic gastritis developing to cancer, changes of gastric mucosal inflammation microenvironment act a important role in occurrence of GC. Helicobacter Pylori (Hp) is one of the major pathogenic factors. As it was recently discovered that Hp infection is closely related to gastric cancer, Hp has been classified as Class I carcinogen by International Agency for Research on Cancer (IARC). Cycloxygenase (COX) protein, a kind of membrane-bound protein with the function of epoxidation and peroxide synthesis, is the rate-limiting enzyme of prostaglandin biosynthesis. COX is consist of two subtypes:COX-1and COX-2. Previous studies revealed that COX-2is related to atrophic gastritis as well as occurrence, development, transfer, differentiation and prognosis of malignancies, including gastric cancer. IL-11, a member of the IL-6 family of cytokines, is a pleiotropic cytokine with anti-inflammatory effects. Recent studies show that IL-11may play a important role in the process of tumorgenesis, even though these studies are insufficient and contradictory in results. Peroxisome Proliferator-Activated Receptor gamma (PPARy), a member of the nuclear receptor superfamily, has a role in regulating gene expression. It is considered the activation of PPARγ has the effect of potential inhibition of tumor. PPARyCoactivator-1(PGC-1) family members are coactivators of PPARy. Researches of the role of PGC-1may be helpful for investigators to understand the relationship between tumor development and cellular energy metabolism-related activities.In order to further reveal the role of inflammatory microenvironment changes after Hp infection during the process of atrophic gastritis to gastric cancer, in this study, we collected gastric mucosal tissues of Hp-infected patients diagnosed definitely by pathological analysis, detected expression levels of COX-2, IL-11and PGC-1and then discuss their interrelationships and application value.Material and methods To collect gastric pathological specimens drawn from gastric antrum with non atrophic gastritis (NAG) and atrophic gastritis diagnosed definitely by gastroscope and pathological analysis. ALL179cases are consist of CSG62cases and CAG117cases including68cases accompanied with IM and49case accompanied with AH (Mild21cases, moderate18cases, severe10cases). All cases had not received anti-Helicobacter pylori therapy and NSAIDs drugs therapy before gastroscopy. RUT is used to detect Hp. After conventional paraffin imbedding and sectioning, all sections were stained with HE and Immunohistochemistry. The expressions of COX-2, IL-11and PGC-1in the tissue were examined respectively under microscope.Result The expression level of COX-2in CAG(Hp+) group is significantly higher than NAG(Hp+) group. There is no significant difference of the expression level of COX-2between CAG(Hp+) group and CAG(Hp-) group. The expression level of PGC-1in CAG(Hp+) group is significantly lower than NAG(Hp+) group. The expression level of PGC-1in CAG(Hp+) group is significantly lower than CAG(Hp-) group. The expression level of IL-11in CAG(Hp+) group is significantly higher than NAG(Hp+) group. The expression level of PGC-1in CAG(Hp+) group is significantly lower than CAG(Hp-) group.Conclusion COX-2, IL-11, PGC-1and Hp infection might play important roles in GC development, with significant correlation among the four factors. Hp infection might involve in carcinogenesis by up-regulating the expression of COX-2. IL-11can be regarded as an early marker of GC development and provide a better targeted therapy to terminate development from CAG to GC. Down-regulation of PGC-1expression may play an essential role in GC development.