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Updated: Jun 13, 2025
The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers
Published on: January 22, 2013
DCS, a novel classifier system based on disulfidptosis reveals tumor microenvironment heterogeneity and guides
Aimin Jiang1, Wenqiang Liu1, Ying Liu1
1Department of Urology, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai, China.
Background:
Emerging evidence suggests that cell deaths are involved in tumorigenesis and progression, which may be treated as a novel direction of cancers. Recently, a novel type of programmed cell death, disulfidptosis, was discovered. However, the detailed biological and clinical impact of disulfidptosis and related regulators remains largely unknown.
Methods:
In this work, we first enrolled pancancer datasets and performed multi-omics analysis, including gene expression, DNA methylation, copy number variation and single nucleic variation profiles. Then we deciphered the biological implication of disulfidptosis in clear cell renal cell carcinoma (ccRCC) by machine learning. Finally, a novel agent targeting at disulfidptosis in ccRCC was identified and verified.
Results:
We found that disulfidptosis regulators were dysregulated among cancers, which could be explained by aberrant DNA methylation and genomic mutation events. Disulfidptosis scores were depressed among cancers and negatively correlated with epithelial mesenchymal transition. Disulfidptosis regulators could satisfactorily stratify risk subgroups in ccRCC, and a novel subtype, DCS3, owning with disulfidptosis depression, insensitivity to immune therapy and aberrant genome instability were identified and verified. Moreover, treating DCS3 with NU1025 could significantly inhibit ccRCC malignancy.
Conclusion:
This work provided a better understanding of disulfidptosis in cancers and new insights into individual management based on disulfidptosis.
Insights
Discovered disulfidptosis, a programmed cell death, is dysregulated in cancers. Targeting disulfidptosis with NU1025 shows promise for treating clear cell renal cell carcinoma (ccRCC), especially a novel subtype.
Area of Science:
- Oncology
- Cell Biology
- Cancer Genomics
Background:
- Cell death pathways are implicated in cancer development and progression.
- Disulfidptosis is a newly identified form of programmed cell death.
- The biological and clinical significance of disulfidptosis and its regulators require further investigation.
Purpose of the Study:
- To investigate the role of disulfidptosis in pan-cancer analysis.
- To explore the biological implications of disulfidptosis in clear cell renal cell carcinoma (ccRCC).
- To identify and validate a novel therapeutic agent targeting disulfidptosis in ccRCC.
Main Methods:
- Pancancer multi-omics analysis (gene expression, DNA methylation, copy number variation, single nucleotide variation).
- Machine learning to decipher disulfidptosis implications in ccRCC.
- Identification and verification of a novel disulfidptosis-targeting agent.
Main Results:
- Disulfidptosis regulators are dysregulated across cancers, linked to DNA methylation and mutations.
- Lower disulfidptosis scores correlate with epithelial-mesenchymal transition.
- Disulfidptosis regulators stratified ccRCC risk, identifying a novel DCS3 subtype with poor prognosis and therapeutic resistance.
- NU1025 treatment inhibited ccRCC malignancy in the DCS3 subtype.
Conclusions:
- This study enhances understanding of disulfidptosis in cancer.
- Provides new insights for personalized ccRCC management based on disulfidptosis.
- Highlights NU1025 as a potential therapeutic agent for specific ccRCC subtypes.
