Abstract
Disulfidptosis, a newly discovered cell death mode distinct from other programmed cell death in lung and kidney cancer cells, is defined as extensive disulfide bonds to actin cytoskeleton proteins, leading to actin contraction and cytoskeletal disruption cell death. New cell death pattern discoveries often drive advances in tumor research. Therefore, the present study attempted to decipher the manifestation and importance of disulfidptosis in pan-cancer. Combining Clinical specimen immunofluorescence staining, single-cell analyses, and spatial transcriptome analyses, we demonstrated the manifestation of disulfidptosis in pan-cancer. Multi-omics analysis has revealed that genomic variants and DNA methylation in DRGs can affect the prognosis of patients with pan-cancer. The nomogram based on the DRGs Score model could accurately predict the prognosis of patients with pan-cancer. PF-562271, EHT-1864, and IPA-3 are potential therapeutic agents targeting disulfidptosis. Collectively, this study deciphered for the first time the importance of disulfidptosis for pan-cancer and developed the DRGs Score model that can assist clinicians in accurately predicting the prognosis and guiding individualized treatment of pan-cancer patients.