• Identified two distinct O-GlcNAcylation-related molecular clusters in gastric cancer with different prognoses and tumor microenvironment profiles.
• Developed a novel prognostic scoring system based on O-GlcNAcylation-related genes that accurately predicts survival and immunotherapy response across multiple cohorts.
• Demonstrated that low-score patients have better prognosis and greater benefit from immunotherapy, validated in a real-world immunotherapy cohort.
• Experimentally verified that ACTA2 promotes gastric cancer cell proliferation and inhibits apoptosis, suggesting a potential therapeutic target.