Supplementary file 1_The mechanical niche in gastric precancer: extracellular matrix remodeling, mechanotransduction, and stem-cell fate.docx

Background<p>The Correa cascade foregrounds infection, inflammation, and epithelial change but does not fully explain how the physical tissue environment influences progression from atrophy to metaplasia and dysplasia.</p>Methods<p>We integrated human observations, gastric organoid and animal perturbation studies, advanced gastric-cancer experiments, and cross-tissue evidence using the Gastric Precancer Mechanobiology Evidence Stratification framework, which ranks evidence by proximity to causal human precancerous mechanics.</p>Results<p>Direct human mechanical measurements remain sparse and methodologically heterogeneous, precluding a universal stiffening trajectory.

YAP has the strongest functional support across gastric regeneration and metaplastic remodeling, integrin–adhesion signaling is convergent but mechanically under-specified, and Piezo1 evidence derives mainly from advanced cancer. Three non-exclusive models—mechanical driver, epithelial-first remodeling, and inflammation-mediated feedback—produce distinct temporal predictions.</p>Conclusion<p>Gastric precancer is best understood through a mechanically extended Correa framework in which static matrix properties, dynamic loading, regional anatomy, inflammatory context, and lineage state jointly determine whether injury resolves or stabilizes abnormal epithelial states.