Molecular Characterization of H. pylori Strains and Biomarkers in Gastric Cancer
Technical Report,01 Jul 2016,30 Jun 2019
The University of Texas Medical Branch at Galveston Galveston United States
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Helicobacter pylori Hp is linked to chronic gastritis, peptic ulcer disease PUD and gastric cancer GC, but it is unknown why diverse gastric diseases develop in different Hp carriers. GC annually claims 700,000 lives worldwide. GC early detection is vital in improving prognosis, but disease biomarkers are lacking. Our goal is to identify gastric epithelial cell GEC responses elicited by GC isolates that could represent candidate biomarkers and unique genomic features of those GC Hp isolates. We used novel human gastroid cultures infected with Hp isolates from diverse gastric diseases. In the first year report we highlighted that infections with different Hp isolates showed by real time PCR distinct expression by GECs of genes related to immunity, NOTCH signaling, metaplasia, cell survival and cell death. In the last year, we examined in depth those results and performed focused studies on the effects of those different GEC responses on the activation of CD4 T cells cocultured with Hp-infected GECs, since Hp subverts host immunity and that may affect tumor immune surveillance. Our studies showed that different Hp isolates not only differ in the host genes that they activate, but also on their influence on T cell responses elicited. Because Notch receptorsligands play key roles in cell differentiation in antigen presenting cells APCs and T cells, we examined their expression in Hp-infected GECs and found that Notch 4 and D114 expression was higher in cells infected with GC isolates compared to PUD and gastritis isolates. Further, these cultures also led to the development of higher T regulatory cells than similar cultures infected with non-cancer Hp strains. The role of Notch 4 in this response was confirmed by siRNA knock-down of Notch 4, which led to a shift in T cell response from T regulatory to Th17.
- Medicine and Medical Research