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Published on: May 12, 2023
Pan-cancer analysis uncovered the prognostic and therapeutic value of disulfidptosis
Yiwei Zhang1,2, Zihua Li2,3, Hengli Lu2
1Department of Laboratory Medicine, The Second People's Hospital of Lianyungang & The Oncology Hospital of Lianyungang, Xuzhou Medical University Lianyungang Second Hospital& Jiangsu University Lianyungang Second Hospitall, No.41, Hailian East Road, Lianyungang, 222006, China.
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.
Insights
Disulfidptosis, a novel cell death, involves disulfide bonds disrupting the actin cytoskeleton. This study reveals its pan-cancer importance and a predictive scoring model for patient prognosis and treatment.
Area of Science:
- Oncology
- Cell Biology
- Cancer Research
Background:
- Disulfidptosis is a newly identified programmed cell death mechanism.
- It is characterized by disulfide bonds linking actin cytoskeleton proteins, causing cell death.
- Understanding novel cell death patterns is crucial for advancing tumor research.
Purpose of the Study:
- To investigate the presence and significance of disulfidptosis across various cancer types (pan-cancer).
- To explore the relationship between genomic alterations, DNA methylation in Disulfidptosis-Related Genes (DRGs), and patient prognosis.
- To develop a predictive model for patient outcomes in pan-cancer.
Main Methods:
- Utilized clinical specimen immunofluorescence staining.
- Employed single-cell and spatial transcriptome analyses.
- Conducted multi-omics analysis including genomic variants and DNA methylation.
Main Results:
- Confirmed the manifestation of disulfidptosis in pan-cancer.
- Identified that genomic variants and DNA methylation in DRGs impact patient prognosis.
- Developed a DRGs Score model demonstrating accurate prognostic prediction for pan-cancer patients.
Conclusions:
- This study elucidates the significance of disulfidptosis in pan-cancer for the first time.
- The developed DRGs Score model aids in predicting prognosis and guiding individualized therapy.
- Potential therapeutic agents targeting disulfidptosis, such as PF-562271, EHT-1864, and IPA-3, were identified.
