The University of Texas Medical Branch at Galveston Galveston United States
Helicobacter pylori Hp is linked to chronic gastritis, peptic ulcer disease PUD and gastric cancer GC, but it is unclear why infected individuals develop different diseases. GC annually claims 700,000 lives worldwide seer.cancer.gov. Early detection of GC is crucial in improving prognosis, but biomarkers of disease are lacking. Our objective is to characterize unique genomic features of GC Hp isolates and gastric epithelial responses elicited by these isolates that could represent candidate biomarkers. We used novel human gastroids infected with a panel of Hp isolates from different gastric diseases. Infections with different Hp isolates revealed by real time PCR distinct expression of genes related to immunity, NOTCH signaling, metaplasia, cell survival and cell death. Isolates from GC and PUD elicited more pronounced changes at the mRNA level compared to uninfected cells. For example, gastroids infected with a GC Hp isolate induced mucin 2, an intestinal mucin, rather than mucin 5AC characteristic of gastric surface cells, which represents neoplastic change in the form of intestinal metaplasia. Flow cytometry confirmed similar changes in protein expression. We noted high expression of immunoregulatory proteins as well as NOTCH receptors and ligands in cells infected with a GC Hp isolate. Thus, additional studies with multiple Hp isolates leading to epithelial responses unique to them and deep genomic sequencing may reveal candidate biomarkers and understanding of potential targets for vaccinetherapy, respectively.