Correlation Of HpSlyD~+ Infection With Wnt Pathway Related Protein Expression In Gastric Mucosal Tissues Of Patients With Different Gastric Diseases

Objective:Investigate the relationships between H.pylori positive and HpSlyD positive bacterial infection and the expressions of Wnt pathway related protein E-cadherin,-catenin and CDX2 in different gastric diseases with biopsy specimens.Then compare the expression of Wnt pathway related proteins in different infection states of H.pylori,aiming to clarify the pathogenicity and possible pathogenesis of HpSlyD positive strains.Methods:1.Tissue samples were obtained from 365 individuals with 81 superficial gastritis?GS?,113 intestinal type atrophic gastritis?GA?or 171 gastric cancer?GC?who participated in the Zhuanghe Gastric Diseases Screening Program between 2008and 2011,including 236 men and 129 women,187 cases?60 years of age and 178cases>60 years of age.2.The above paraffin embedded tissue sections were used to extract the DNA of paraffin embedded tissues using a WaxFree^TMDNA Kit.3.The conserved genes?16s rRNA,glmM?of H.pylori were amplified by PCR amplification,and the conserved regions of HpslyD gene were amplified by PCR amplification in H.pylori positive population.4.Formalin-fixed,paraffin-embedded tissues were immunohistochemically?IHC?stained using the avidin-biotin complex method as described.Results:CDX2 and TCF4 were mainly expressed in nucleus,ECAD was mainly in cell membrane,and?-catenin could express in cell membrane and cytoplasm.In superficial gastritis group,the expression of ECAD was significantly higher than in Hp positive group than that in the Hp negative group.And the expression of CDX2was significantly higher in HpslyD+group than in HpslyD-group.While there were no statistically differences for TCF4,?-catenin membrane,?-catenin cytoplasm in either of the compared group.In the atrophic gastritis group,for the Hp+and Hp-groups,there were no significant differences in the expression of all the proteins,but there were significant differences in the expression of CDX2 and?-catenin membrane.In the gastric cancer group,the expression of CDX2 was significant in both the Hp+vs Hp-group and the HpslyD+vs HpslyD-group.TCF4 and?-catenin were overexpressed in HpslyD+group and downregulated in HpslyD-group.For the intestinal gastric cancer patients,CDX2 and?-catenin were overexpressed,while for the diffuse gastric cancer patients,CDX2?TCF4 and?-catenin membrane were overexpressed.When infected by HpSlyD,the expression of all the protein mentioned in the wnt pathway were overexpressed in GS vs GA,which was higher in the GA group.For the GS vs GC group,the differences were statistically significant for the expressions of CDX2?TCF4 and?-catenin membrane.Conclusion:1.HpSlyD is a virulence factor in the progression of gastric disease.It can promote gastric mucosal atrophy and carcinogenesis through CDX2.2.HpSlyD may promote intestinal metaplasia through ECAD.3.HpSlyD may promote intestinal metaplasia and carcinogenesis of gastric mucosa through?-catenin,especially the occurrence of intestinal GC.4.HpSlyD may promote the development of gastric cancer,especially diffuse gastric cancer,through TCF4.