Research progress on molecular mechanism of pyroptosis caused by Helicobacter pylori in gastric cancer

Abstract

Gastric cancer (GC) is a prevalent malignancy worldwide. Helicobacter pylori (H. pylori), a Gram-negative spiral bacterium, has the ability to colonize and persist in the human gastric mucosa. Persistent H. pylori infection has been identified as a major risk factor for ~80% of GC cases. The interplay between H. pylori pathogenicity, genetic background, and environmental factors collectively contribute to GC transformation. Eradicating H. pylori infection is beneficial in reducing the recurrence of gastric cancer and residual cancer. However, the underlying molecular mechanisms involved in GC remain incompletely understood. Additionally, H. pylori reshapes the immune microenvironment within the stomach which may compromise immunotherapy efficacy in infected individuals. Clinical eradication of H. pylori infection still faces numerous challenges. In this review, the authors summarize recent research progress on elucidating the molecular mechanisms underlying H. pylori infection in GC development. Notably, CagA protein—a carcinogenic virulence factor predominantly expressed by Asian strains of H. pylori—induces inflammation and excessive ROS production within gastric mucosa cells. Dysregulation of multiple pyroptosis signalling pathways can lead to malignant transformation of these cells. MiRNA-1290 plays a crucial role in GC initiation and progression while serving as an indicator for disease progression dynamics. Pyroptosis exhibits dual roles both promoting carcinogenesis and inhibiting tumour growth; thus it holds potential clinical applications for drug-resistant GC treatment strategies. Furthermore, pyroptosis may play a regulatory role within the immune system during gastric cancer development. Lastly, the authors provide an overview on current concepts regarding pyroptosis as well as insights into miRNA-1290’s pathogenicity and clinical value within immune mechanisms associated with GC, aiming to serve as reference material for researchers.