A Genetic and Immunohistochemical Analysis of H. Pylori Phenotypes and p27 expression in Adenocarcinoma Patients in Jordan

Abstract

Stomach (gastric) cancer is one of the most prevalent and deadly cancers worldwide and the vast majority of gastric cancers are adenocarcinomas. Based on prior research, there is an association between Helicobacter pylori (H. pylori) infection and the frequency of duodenal ulcer, distal gastric adenocarcinoma, mucosa-associated lymphoid tissue lymphoma, and antral gastritis. H. pylori virulence and toxicity factors have been identified to significantly influence the clinical outcomes of H. pylori infection and gastric adenocarcinoma. However, it is unclear exactly how different strains of H. pylori infection affect gastric adenocarcinoma. Current research suggests this involves tumor suppressor genes, like p27, but also H. Pylori toxic proteins. Therefore, we quantified known H. Pylori genotypes within adenocarcinoma patients to establish the prevalence of known toxins that include cytotoxin-associated gene A (cagA) and vacuolating cytotoxin A (vacA) within patients of variable diagnosis. This analysis used gastrectomy samples which were validated for DNA viability. The incidence of H. Pylori in adenocarcinoma patients in Jordan was established to be 54.5% positive (ureA gene) with cagA genotype occurrence at 57.1% but also vacA gene ratios 24.7%:22.1%: 14.3%:14.3%. (vacAs1:vacAs2: vacAm1:vacAm2). We found statistically significant evidence that p27 was dysregulated and suppressed within nearly all H. Pylori vacA genotypes but also that 24.6% of H. Pylori samples analyzed had a different bacterial genotype and curiously that p27 protein expression was retained in 12% of tested adenocarcinoma H. Pylori samples. This is suggestive that p27 could be used as a prognostic indicator but also that an unknown genotype could be contributing to the regulatory effects of p27 protein within this bacterial and cellular environment. Key ContributionIn Jordan, this is the first retrospective study to use validated viable gastrectomy tissue samples rather than tissue biopsies to characterize each of the currently defined H. pylori strains in patients with variable gastric cancer diagnosis whilst also comparing results with p27 expression within 8 years using these laboratory techniques. ConclusionsBased on these results, a reduction in p27 expression in H. pylori-infected men and women of all ages may be associated with the occurrence of gastric adenocarcinomas. Therefore, p27 may represent a key diagnostic marker and predictor of adenocarcinoma prognosis in such individuals and may find use for guiding subsequent treatment decisions.