Transcriptome analysis of primary gastric cancer cells infected with EastAsian and Western strains of Helicobacter pyloriWestern_1
To understand the difference in pathogenic mechanisms between EastAsian and Western strains of Helicobacter pylori (H. pylori), we compared, analyzed, and verified the differentially expressed genes (DEGs) obtained from primary gastric cancer cells infected with EastAsian and Western strains of H. pylori. The primary gastric cancer cells were infected with the EastAsian strain (GZ7) and the Western strain (26695) of H. pylori for 6 hours at MOI 50:1 and then collected for transcriptome sequencing. DEGs were screened with |Log2FoldChange| >1 and FDR  0.05. Bioinformatics analysis of the DEGs was performed using the online Omicsbean-Cancer tool. Four genes of the DEGs were selected for further analysis by the TCGA database and validated by Western blot. There were 31 DEGs between the H. pylori GZ7-infected and uninfected gastric cancer cells and 109 DEGs between the H. pylori 26695-infected and uninfected gastric cancer cells; Twenty-two DEGs were shared between H. pylori GZ7 and H. pylori 26695-infected groups; Nine DEGs were present only in H. pylori GZ7 groups, and 87 DEGs present only in H. pylori 26695 groups. These DEGs were mainly involved in inflammation, cell adhesion, cell surface receptors, NF-B, TNF signaling pathways, lipid, amino acid metabolism, and so on. Western blot analysis confirmed that H. pylori   infection up-regulated the expression of transcription factors JUN, FOSL1, IL6 and DKK1 (only present in the H. pylori GZ7 group) proteins in gastric cancer cells, and knockdown of JUN gene in cells suppressed the expression of IL6 and DKK1. When H. pylori GZ7 was used to re-infect JUN-knockdown and control cells, protein expression of JUN, IL6 and DKK1 was restored. Analysis of the TCGA database revealed that IL6 and DKK1 mRNA were significantly higher(P<0.001), higher expression of IL6 and DKK1 was negatively associated with a 10-year survival rate of gastric cancer patients (P<0.03). In conclusion, there is a clear difference in the DEGs generated by gastric cancer cells infected with the EastAsian and Western strains of H. pylori, which may be one of the reasons for the difference in the incidence of gastric cancer between EastAsian and Western countries.