Molecular mechanism of microplastic intake promoting gastric epithelial cell carcinogenesis.

We aimed to explore the effects and mechanisms of MPs on GEC carcinogenesis. Gastric tissues from four adjacent healthy controls and four patients with GC were analyzed for MPs using Raman spectroscopy and Py-GC/MS, alongside proteomic and metabolomic analyses. A series of molecular biology techniques were used for corresponding validation. IHC and IF were used to assess the expression levels of SDHA, EMT-related proteins and CD44 in the gastric tissues of nude mice. Single-cell sequencing was used to examine SDHA and CD44 expression. Eleven types of MPs were identified in both GC and normal control gastric tissue samples. Omics analysis identified SDHA as differentially expressed, with lower expression in GC tissues, while EMT-related proteins and CD44 were increased in GC tissues. PS enhanced GES-1 cell activity and migration, and increased reactive oxygen species levels. After 8 weeks of exposure, focal gastric epithelial dysplasia was observed in PS-exposed mice. PS-fed mice exhibited increased expression of EMT-related proteins and CD44, and decreased SDHA expression in gastric tissues. Single-cell sequencing data were used to observe the possible co-expression of SDHA and CD44 in gastric cells. These findings associate experimental PS exposure with gastric epithelial stress and phenotypic changes and identify SDHA as a candidate metabolic regulator. Further functional studies are needed to determine whether these changes contribute to gastric neoplastic progression.