Inflammation as a Mediator of Microbiome Dysbiosis-Associated DNA Methylation Changes in Gastric Premalignant Lesions

Evidence for the influence of chronic inflammation induced by microbial dysbiosis on aberrant DNA methylation supports a plausible connexion between disordered microbiota and precancerous lesions of gastric cancer(PLGC).Here,a comprehensive study including multi-omics data was performed to estimate the relationships amongst the gastric microbiome,inflammatory proteins and DNA methylation alterations and their roles in PLGC development.The results demonstrated that gastric dysbacteriosis increased the risk of PLGC and DNA methylation alterations in related tumour suppressor genes.Seven inflammatory biomarkers were identified for antrum and corpus tissues,respectively,amongst which the expression levels of several biomarkers were significantly correlated with the microbial dysbiosis index(MDI)and methylation status of specific tumour suppressor genes.Notably,mediation analysis revealed that microbial dysbiosis partially contributed to DNA methylation changes in the stomach via the inflammatory cytokines C-C motif chemokine 20(CCL20)and tumour necrosis factor receptor superfamily member 9(TNFRSF9).Overall,these results may provide new insights into the mechanisms that might link the gastric microbiome to PLGC.

Effects of folic acid on epithelial apoptosis and expression of Bcl-2 and p53 in premalignant gastric lesions

AIM: To evaluate the effects of folic acid on epithelial apoptosis and expression of Bcl-2 and p53 in the tissues of premalignant gastric lesions. METHODS: Thirty-eight patients, with premalignant gastric lesions including 18 colonic-type intestinal metaplasia (IM) and 20 mild or moderate dysplasia, were randomly divided into a treatment group (n = 19) receiving folic acid 10 mg thrice daily and a control group (n = 19) receiving sucralfate 1 000 mg thrice daily for 3 mo. All patients underwent endoscopies and four biopsies were taken prior to treatment and repeated after concluding therapy. Folate concentrations in gastric mucosa were measured with chemiluminescent enzyme immunoassay. Epithelial apoptosis and the expression of Bcl-2 and p53 protein in gastric mucosa were detected with flow cytometric assay. RESULTS: The mean of folate concentration in gastric mucosa was 9.03±3.37 μg/g wet wt in the folic acid treatment group, which was significantly higher than 6.83±3.02 μg/g wet wt in the control group. Both the epithelial apoptosis rate and the tumor suppressor p53 expression in gastric mucosa significantly increased after folic acid treatment. In contrast, the expression of Bcl-2 oncogene protein decreased after folic acid therapy. CONCLUSION: These data indicate that folic acid may play an important role in the chemoprevention of gastric carcinogenesis by enhancing gastric epithelial apoptosis in the patients with premalignant lesions.

The role of computer-assisted systems for upper-endoscopy quality monitoring and assessment of gastric lesions

This article analyses the literature regarding the value of computer-assisted systems in esogastroduodenoscopy-quality monitoring and the assessment of gastric lesions.Current data show promising results in upper-endoscopy quality control and a satisfactory detection accuracy of gastric premalignant and malignant lesions,similar or even exceeding that of experienced endoscopists.Moreover,artificial systems enable the decision for the best treatment strategies in gastriccancer patient care,namely endoscopic vs surgical resection according to tumor depth.In so doing,unnecessary surgical interventions would be avoided whilst providing a better quality of life and prognosis for these patients.All these performance data have been revealed by numerous studies using different artificial intelligence(AI)algorithms in addition to white-light endoscopy or novel endoscopic techniques that are available in expert endoscopy centers.It is expected that ongoing clinical trials involving AI and the embedding of computer-assisted diagnosis systems into endoscopic devices will enable real-life implementation of AI endoscopic systems in the near future and at the same time will help to overcome the current limits of the computer-assisted systems leading to an improvement in performance.These benefits should lead to better diagnostic and treatment strategies for gastric-cancer patients.Furthermore,the incorporation of AI algorithms in endoscopic tools along with the development of large electronic databases containing endoscopic images might help in upper-endoscopy assistance and could be used for telemedicine purposes and second opinion for difficult cases.