Integrated Genomic Analysis Identifies Clinically Relevant Molecular Subtypes and Disulfidptosis-Related Prognostic Signature of Gastric Cancer

Disulfidptosis is a newly defined disulfide stress-induced cell death. However, there are gaps in the prognostic role of disulfidptosis-related genes (DRGs) and their correlation with the tumor microenvironment (TME) in gastric cancer (GC). In here, we systematically investigated DRG changes at genomic and transcriptional levels, prognostic value, and their expression patterns in GC. Fifteen DRGs were used to identify the different subtypes, and the differences in prognosis and immune infiltration among the subtypes were examined. We identified 3 distinct molecular subtypes and observed profound differences among the 3 subtypes in clinical outcomes and infiltrating immune cells. Subsequently, a disulfidptosis-related signature (DRG_score) was constructed based on the overlapped disulfidptosis phenotype-related differentially expressed genes and was verified in an external cohort. The multivariate analysis confirmed that the DRG_score serves as an independent prognostic indicator for GC, and then a nomogram was built to increase the clinical applicability of the DRG_score. Furthermore, significant variations were observed in the TME, expression of multiple immune checkpoints, microsatellite status, tumor mutational burden, and response to different chemotherapeutics among the 2 DRG_score groups. A low DRG_score implies more significant TME cell infiltration and better response to immunotherapy. In conclusion, we present a comprehensive overview of the DRG profile in GC and develop a novel signature for GC patients. These findings could help us better understand DRG in GC and provide a theoretical foundation for future studies targeting disulfidptosis in GC.