| Gastric cancer is the second leading cause of cancer deaths worldwide, and in the USA mortality is higher among minority populations. The majority of human stomach tumors are associated with chronic infection with bacterial pathogen Helicobacter pylori. Helicobacter pylori is a Gram-negative microaerophilic bacterium that colonizes the gastric mucosa, leading to disease conditions ranging from gastritis to cancer. It is the highest identified risk factor for the development of gastric cancer and is thus considered as a Class I Carcinogen.;Our aim was to explore the host factors contributing to H.pylori caused gastric cancer. Studies shows that Myd88 a key immunomodulator is essential for H. pylori induction of all cytokines except alpha interferon (IFN--f--n--f--N). We hypothesized that persistent activation of myeloid differentiation primary response gene 88 (MyD88) signaling by H. pylori during chronic inflammation contributes to gastric carcinogenesis. To address this hypothesis we established a mouse model of gastric cancer to investigate gene expression during the course of Helicobacter infection using wild type (WT) and MyD88 deficient mice (MYD88KO). The mouse model result suggests that loss of the myeloid differentiation gene (MyD88), contributes to gastric carcinogenesis. To analyze the gene expression dataset, statistical and bioinformatics tools were used. We found a high number of differentially regulated genes during infection in MyD88 KO mice as compared to WT mice. Among the top 50 highly induced genes included those involved in tissue remodeling, cell communication and cytoskeletal properties. Our data suggest that tissue remodeling with chronic inflammation may play an important role in gastric cancer development and progression. Further evaluation of microarray data using Gene Ontology (GO) revealed important pathways including apoptosis, IGF-receptor and longevity and Adipocytokine signaling pathway. The identification of these host factors could potentially serve as targets for disease prevention and provide a basis for future studies on Helicobacter-induced gastric carcinogenesis. |
