Molecular Mechanisms and Biomarkers Driving the Transition From Chronic Atrophic Gastritis to Gastric Cancer

Abstract

Gastric cancer continues to be a major contributor to global cancer morbidity and mortality. Although the Correa cascade is widely used as a model for gastric carcinogenesis, the molecular mechanisms driving the transition from chronic atrophic gastritis to invasive cancer have not been comprehensively integrated into a unified molecular framework. This review aims to synthesize current knowledge of the molecular events associated with each stage of the Correa cascade and to evaluate the clinical relevance of established and emerging biomarkers for risk stratification, early diagnosis, and personalized surveillance. This review summarizes the principal molecular mechanisms involved in the progression from chronic gastritis through chronic atrophic gastritis, intestinal metaplasia, dysplasia, and ultimately gastric cancer. These mechanisms include inflammatory cytokine networks, epigenetic modifications, genomic instability, disruption of signaling pathways, clonal evolution, and remodeling of the tumor microenvironment. Particular emphasis is placed on contemporary tissue and circulating biomarkers, their diagnostic and prognostic significance, and the application of advanced technologies including multi-omics analysis, spatial transcriptomics, single-cell sequencing, and liquid biopsy. The available evidence supports a conceptual model of gastric carcinogenesis as a continuous molecular evolutionary process in which chronic inflammation initiates progressive epigenetic and genetic alterations that promote clonal selection and malignant transformation. Integrating molecular biomarkers with conventional morphological assessment may improve risk stratification, facilitate earlier detection of disease progression, and support the implementation of personalized strategies for gastric cancer prevention, surveillance, and treatment.