Metabolomic biomarkers discovery across chronic gastritis to gastric cancer progression

Gastric cancer (GC) is a severe malignancy characterized by late diagnosis, poor prognosis, and low survival rates. Its progression is often linked to chronic non-atrophic gastritis (CNAG) and chronic atrophic gastritis (CAG), which show atypical symptoms. Identifying biomarkers for CNAG, CAG, and GC progression is crucial for earlier diagnosis and prevention. This study conducted non-targeted metabolomics on 81 clinical samples (17 controls; 23, 23, and 18 from CNAG, CAG, and GC patients, respectively) using ultra-high-performance Liquid chromatography and high-resolution mass spectrometry. A total of 763 metabolites were identified, of which eight metabolic pathways were in dysregulation at different disease stages. Disease progression showed pronounced disruptions in amino acid, Lipid, and microbial metabolism. Targeted metabolomics identified 56 metabolites, with significant differences in O-(4,8-dimethylnonanoyl) carnitine and dehydroepiandrosterone sulfate (DHEAS). DHEAS and L-threonic acid (L-TA) were validated as biomarkers, with detection methods developed and applied to confirm their clinical significance. These findings enhance understanding of CNAG, CAG, and GC progression and provide validated biomarkers for potential clinical application in GC diagnosis and treatment.