Background The specific role of glutamine metabolism in stomach adenocarcinoma (STAD) remains incompletely understood. Methods To examine the involvement of glutamine metabolism in STAD, we used R software to perform clustering and prognostic analyses based on glutamine metabolism‐related genes (GMGs). A glutamine metabolism‐related signature was constructed and evaluated in multiple cohorts. We further investigated the functional role of GLUD2 in gastric cancer cells using colony formation, wound‐healing, and transwell assays to assess proliferation, migration, and invasion, and western blotting to measure GLUD2 protein expression. Results Based on GMG expression profiles, STAD patients were divided into two subgroups with distinct prognostic, immune, and biological pathway characteristics. Using three prognosis‐associated GMGs, we developed a glutamine metabolism‐related prognostic signature that provided effective risk stratification and was associated with differences in immune cell infiltration, mutation landscapes, and survival between high‐ and low‐risk groups. Notably, GLUD2, a glutamine metabolism‐related enzyme, was upregulated in STAD and associated with unfavorable clinicopathological features. Functional assays showed that GLUD2 knockdown inhibited, whereas GLUD2 overexpression enhanced, the proliferation, migration, and invasion of gastric cancer cells. Conclusion Glutamine metabolism‐related patterns are associated with prognosis, tumor mutation burden, immune cell infiltration, and predicted response to therapy in STAD. GLUD2 appears to promote malignant phenotypes of STAD cells and may represent a potential therapeutic target related to glutamine metabolism, although further mechanistic and in vivo studies are needed to validate these findings.
Ge et al. (Thu,) studied this question.