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

Abstract

Gastric cancer (GC) is a prevalent malignancy worldwide. <i>Helicobacter pylori</i> (<i>H. pylori</i>), a Gram-negative spiral bacterium, has the ability to colonize and persist in the human gastric mucosa. Persistent <i>H. pylori</i> infection has been identified as a major risk factor for ~80% of GC cases. The interplay between <i>H. pylori</i> pathogenicity, genetic background, and environmental factors collectively contribute to GC transformation. Eradicating <i>H. pylori</i> 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, <i>H. pylori</i> reshapes the immune microenvironment within the stomach which may compromise immunotherapy efficacy in infected individuals. Clinical eradication of <i>H. pylori</i> infection still faces numerous challenges. In this review, the authors summarize recent research progress on elucidating the molecular mechanisms underlying <i>H. pylori</i> infection in GC development. Notably, CagA protein-a carcinogenic virulence factor predominantly expressed by Asian strains of <i>H. pylori</i>-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.