Metabolic and immune‐related gene signatures: Predictive stratification and prognostic implications in gastric cancer

Abstract Background Gastric cancer, marked by its heterogeneous nature, showcases various molecular subtypes and clinical trajectories. This research delves into the significance of metabolic and immune‐driven pathways in gastric cancer, constructing a prognostic signature derived from differentially expressed metabolic and immune‐correlated genes (DE‐MIGs). Methods Metabolic and immune‐associated gene were sourced from the GeneCards database. Differential expression analysis on the TCGA‐STAD dataset was executed using the limma package, unveiling 51 DE‐MIGs that underwent functional enrichment scrutiny. The LASSO Cox regression methodology guided the creation of the prognostic signature, and individual patient risk scores were determined. Assessment tools like CIBERSORT, ESTIMATE and ssGSEA were deployed to study the immune microenvironment, while mutation profiles, genomic stability, resistance to chemotherapy and immunotherapy responsiveness were scrutinized across distinct signature categorizations. Results Among the identified DE‐MIGs, 26 were significantly tied to the overall survival of gastric cancer patients. The developed prognostic signature proficiently differentiated patients into high‐risk and low‐risk cohorts, with the latter showing markedly better outcomes. The study underscored the centrality of the immune microenvironment in influencing gastric cancer outcomes. Key pathways such as TGF‐Beta, TP53 and NRF2 dominated the high‐risk group, whereas the LRTK−RAS and WNT pathways characterized the low‐risk group. Interestingly, the low‐risk segment also manifested a heightened tumor mutation burden and enhanced susceptibility to immunotherapy. Conclusions Our findings introduce a pivotal prognostic signature, rooted in DE‐MIGs, that effectively segregates gastric cancer patients into distinct risk‐based segments. Insights into the influential role of the immune microenvironment in gastric cancer progression pave the way for more refined therapeutic interventions.