Expression Of CYLD In Gastric Cancer And Dysplasia And Its Correlation With Helicobacter Pylori CagA

BACKGROUND:As one of the most common tumors in the digestive system,gastric cancer has become a global problem affecting human health.There are large geographical differences in the incidence of gastric cancer.The incidence in East Asian countries such as China,South Korea,and Japan is eight times that of North America,accounting for more than half of the total number of patients with gastric cancer in the world.The Helicobacter pylori infection rate in these countries is also higher than in Western countries.Cytotoxin-related gene A(CagA)is one of the important virulence factors secreted by Helicobacter pylori,and its positive strains have a significantly greater risk of serious clinical consequences after infection than negative strains.Evidence-based medical evidence indicates that the CagA-positive strain increases the risk of gastric cancer compared to the CagA-positive strain.Studies on the carcinogenic mechanism of CagA have shown that CagA can inactivate or reduce the expression of various tumor suppressor genes,thereby hindering its function.Familial Cylindroma(CYLD)protein is a kind of deubiquitinating enzyme.It regulates cell function through deubiquitinating a variety of signaling molecules and mediates processes such as cell movement,immune response,and inflammatory response.Studies have shown that CYLD plays a role in gastric cancer as a tumor suppressor,and inactivating tumor suppressor genes is one of the carcinogenic mechanisms of H.pylori,so we speculate that the expression of CYLD may be affected by H.pylori infection and CagA protein,Which is related to the occurrence and development of gastric cancer.PURPOSE:Detect the expression of CYLD and its correlation with CagA protein in gastric cancer and dysplasia,to explore the role of CagA and CYLD in the development of gastric cancer.METHOD:A total of 81 cases of newly diagnosed and surgically removed gastric cancer tissues from Huaihe Hospital of Henan University from July 1,2018 to December 31,2019 were selected.During the same period,endoscopic examination and gastric biopsy were selected in our hospital.In the same period,47 cases of dysplasia and 78 cases of chronic gastritis were selected for endoscopic examination and gastric biopsy in our hospital.All tissue specimens were fixed with paraformaldehyde solution,made into wax blocks and stored in the pathology department.The diagnosis of HP infection was performed by 13 C urease breath test,rapid urease test and tissue toluidine blue staining.At least two positive results are diagnosed as HP infection.According to the Helicobacter pylori infection,the components were divided into HP positive group and HP negative group.The expression of CagA in HP positive group was detected by immunohistochemistry,and the HP positive group was divided into CagA-positive group and CagA-negative group according to their expression.Immunohistochemical method was used to detect the expression of CYLD in each group.The correlation of CYLD expression with HP infection and CagA was analyzed by Statistical processing methods,as well as the relationship between CagA protein and clinical case data of gastric cancer patients(age,gender,Lauren classification,degree of differentiation,Lymph node metastasis,TNM stage).RESULT:1.The expression of CagA protein of HP infected patients in three groups : gastric cancer group(82.8%)> dysplasia group(72.7%)> chronic gastritis group(49.1%),the difference between the three groups was significant(P <0.001).Compared with each other,the expression of CagA in tissues of gastric cancer and dysplasia was higher than that of chronic gastritis(P <0.001,P = 0.030),but there was no statistically significant difference between gastric cancer and dysplasia(P > 0.05).2.The relationship between CagA and clinicopathological data of gastric cancer: the expression of CagA is related to Lauren classification,degree of differentiation,lymph node metastasis,Tumor stage,and has nothing to do with age and gender.The expression of CagA was higher in intestinal gastric cancer,poorly differentiated gastric cancer,with lymph node metastasis,advanced gastric cancer(stage III-IV)than diffuse gastric cancer,moderately and highly differentiated gastric cancer,no lymph node metastasis and early gastric cancer(stage I-II).It has statistical significance(P <0.05).3.The expression of CYLD in in three groups: chronic gastritis group(71.8%)> dysplasia group(55.3%)> gastric cancer group(35.8%),the difference between the three groups was significant(P <0.001).Compared with each other,the expression of CYLD in gastric cancer group and dysplasia group was significantly lower than that in chronic gastritis.Statistical significance(P = 0.808).The expression of CYLD in the HP positive chronic gastritis group(67.9%),HP positive dysplasia group(45.5%),and HP positive gastric cancer group(27.6%)gradually decreased,and the difference was statistically significant(P <0.001).4.The relationship between CYLD and HP infection: CYLD expression in HP positive group was lower than that in HP negative group,the difference was statistically significant(P = 0.001).Within the group,in the gastric cancer and dysplasia groups,the CYLD expression in the HP-positive subgroup was lower than that in the HP-negative subgroup,and the differences were statistically significant(P = 0.014,P = 0.037).But there was no significant difference in the expression of CYLD between the HP positive subgroup and the HP negative subgroup in the chronic gastritis group(P> 0.05).5.The relationship between CYLD and CagA: in gastric cancer group and dysplasia group,the expression of CYLD in CagA-positive HP infected patients was lower than that in CagA-negative HP infected patients,the difference was statistically significant(P = 0.001,P = 0.004).In the chronic gastritis group,there was no statistical difference in the expression of CYLD between CagA-positive HP infection and CagA-negative HP infection(P> 0.05).CYLD expression in gastric cancer group and dysplasia group was negatively correlated with CagA protein(r =-0.433,P = 0.001;r =-0.534,P = 0.004).CONCLUSION:1.The expression of Helicobacter pylori CagA protein is increased in dysplasia and gastric cancer,and is closely related to gastric cancer classification,staging and lymph node metastasis,suggesting that CagA may be involved in the whole process of gastric cancer development.2.The expression of CYLD is reduced in dysplasia and gastric cancer,which may play a role in inhibiting the occurrence of gastric cancer.3.The expression of CYLD in dysplasia and gastric cancer is negatively correlated with CagA,suggesting that there is an interaction between them in the occurrence of gastric cancer.The down-regulated expression of CYLD may be one of the carcinogenic mechanisms of CagA-positive Helicobacter pylori.