Prognostic and therapeutic potential of disulfidptosis-related genes in colon adenocarcinoma: a comprehensive multi-omics study.

BACKGROUND: Disulfidptosis-related genes (DRGs) have emerged as key players in the prognosis of colon cancer(CC) and hold promise as potential therapeutic targets. This study systematically evaluates their prognostic significance and explores their potential for therapeutic intervention in colon adenocarcinoma. METHODS: Colon adenocarcinoma(COAD) samples were categorized based on DRG expression to analyze differences in the immune landscape across molecular subtypes. Variations between high-risk (HRG) and low-risk (LRG) groups and changes in cell population dynamics across different stages were examined. The expression patterns of Diaphanous-Related Formin 1 (DIAPH1) and NADH: Ubiquinone Oxidoreductase Subunit B10 (NDUFB10), key components of the prognostic model, were assessed during T cell development. The model was validated using external datasets, and single-cell analysis was performed to investigate spatial distribution differences in tumor-infiltrating cell populations. RESULTS: DRGs were critical in modulating T cell differentiation in COAD. DIAPH1 and NDUFB10 showed significant fluctuations during T cell development, indicating their involvement in immune regulation. Single-cell analysis revealed distinct spatial distribution patterns between T cells and epithelial cells. The ProjecTILs algorithm identified a higher proportion of Th1 cells, while Graph Convolutional Network (GCN) analysis showed no significant differences in T cell subtype proportions across different phenotypes. In vitro experiments further demonstrated that the knockdown of DIAPH1 and NDUFB10 in T cells effectively inhibited tumor proliferation. CONCLUSION: The DRG-based prognostic model demonstrated strong predictive power in COAD, highlighting the potential of DRGs as therapeutic targets. These findings provide a solid foundation for developing novel treatment strategies targeting disulfide ptosis pathways in CC.