Comparative Genomics Profiling In Gastric Epithelial Cell Line GES-1 Induced By Different Clinical Isolates Of Helicobacter Pylori

The incidence of gastric cancer is in the second place in various cancers in China. It is a serious harm to the health of people. From 80 years in the 20th century, the relation of gastric cancer and H. pylori, which has a high infection, received extensive attention. Epidemiology confirmed that chronic infection of H. pylori was an important risk factors for gastric cancer, and the risk of infected people suffering from gastric cancer was 4 times higher than non-infected. Many researches showed that there was the mode of "chronic gastritis-gastric atrophy intestinal metaplasia-dysplasia-gastric cancer" and H. pylori played a leading role. In 1998, Watanabe reported that Mongolian gerbil infected by H. pylori could have gastric cancer for the first time. In 1994, IARC of the World Health Organization made H. pylori as a class I carcinogen. But the mechanism of gastric cancer caused by H. pylori has not fully understood.The incidence of gastric cancer is a multi-cause, multi-stage process. Infected by H. pylori, it may lead to chronic gastritis or gastric cancer. It indicates that different strains may have different effects on gastric epithelial cells and cause different diseases.The experiment used 20 strains respectively isolated from the patients with gastric cancer and gastritis. The strains were co-cultured in different concentration ratio with GES-1 cells. The cells were collected after 12,24 and 48 hours and checked by MTT and flow cytometry. The result showed that H. pylori strains from different sources had a significant difference on the proliferation of GES-1 cells. Low concentrations of H. pylori can promote the proliferation of cells in different degrees and high concentrations can inhibit the proliferation. As time goes by, the activity of promoting of low concentrations in proliferation increased gradually, so as the inhibiting of high concentrations. H. pylori strains from different sources can cause the apoptosis of gastric epithelial cells increased, but there was no significant difference. As the concentrations and time increased, H. pylori strains had more significant effect on the apoptosis of gastric epithelial cells.The two H. pylori strains, which had the most significant and least effect on the proliferation and apoptosis of GES-1 cells, were selected and co-cultured with GES-1 cells. The tRNA products were extracted after the cells were collected, and then the whole-genome microarray hybridization were analyzed. The results showed that GES-1 cells infected by H. pylori can cause extensive changes on gene expression of gastric epithelial cells. These differentially expressed genes related with activation and inactivation of proto-oncogenes and tumor suppressor gene, cell cycle, movement of cytoskeleton, apoptosis, DNA synthesis, transcription, cell signaling, protein translation, material and energy metabolism and so on. Some genes closely related with cancer, such as ETS1,JUN,JUNB,CLDN1,CXCL2,IRAK2,NUPR1,STC2,TP53BP1,TNFAIP3,TRAF1,DIO2,ST13 and SR protein family, were filtered out for further researches of gene expression and biological function.