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Pan-cancer genetic analysis of disulfidptosis-related gene set
1Yinuo Biomedical Co., Ltd, Tianjin, China.
Background:
A recent study has identified a novel programmed cell death pathway, termed disulfidptosis, which is based on disulfide proteins. This discovery provides new insight into the mechanisms of cell death and may have implications for therapeutic strategies targeting cell death pathways. This study aimed to evaluate the pan-cancer genomics and clinical association of disulfidptosis and disulfidptosis-related cell death genes, including SLC7A11, INF2, CD2AP, PDLIM1, ACTN4, MYH9, MYH10, IQGAP1, FLNA, FLNB, TLN1, MYL6, ACTB, DSTN, and CAPZB.
Methods:
Using multi-omics profiling data, this study provides a comprehensive and systematic characterization of disulfidptosis genes across more than 9000 samples of over 30 types of cancer.
Results:
FLNA and FLNB were the two most frequently mutated disulfidptosis cell death genes in cancer. UCEC and SKCM were the two cancer types that have the highest mutation rates while the mutation of ACTN4 was associated with worse survival of CESC and ESCA. Breast cancer was potentially affected by disulfidptosis because its subtypes are different in disulfidptosis gene expression. Similarly, KIRC might also be associated with disulfidptosis. Additionally, the association of disulfidptosis-related cell death genes with survival was analyzed, with MESO and LGG as the top cancer types with survival associated with disulfidptosis cell death genes. The correlation between CNV and survival across multiple cancer types found that UCEC, KIRP, LGG, and KIRC were the top cancer types where the CNV level was associated with survival. There was a negative correlation between expression and methylation for most of the genes and there was only a slight correlation between methylation levels and survival of cancer in LGG. About half of the disulfidptosis-related cell death proteins were associated with the activation of EMT. Disulfidptosis genes were correlated to immune cell infiltration levels in cancers. Multiple compounds were identified as potential drugs that might be affected by disulfidptosis-related cell death for future study.
Conclusion:
Disulfidptosis cell death genes are potentially involved in many cancer types and can be developed as candidates for cancer diagnosis, prognosis, and therapeutic biomarkers.
Insights
A novel cell death pathway, disulfidptosis, involving disulfide proteins was identified. This pathway and its related genes show potential as cancer diagnostic, prognostic, and therapeutic biomarkers across various cancer types.
Area of Science:
- Cell Biology
- Cancer Genomics
- Molecular Mechanisms of Cell Death
Background:
- A new programmed cell death pathway, disulfidptosis, has been identified, driven by disulfide proteins.
- This discovery offers novel insights into cell death mechanisms and potential therapeutic targets.
- The study focuses on disulfidptosis and its associated genes, including SLC7A11, INF2, and FLNA.
Purpose of the Study:
- To conduct a pan-cancer genomic and clinical association analysis of disulfidptosis and related genes.
- To systematically characterize disulfidptosis genes across diverse cancer types using multi-omics data.
Main Methods:
- Utilized multi-omics profiling data from over 9000 cancer samples across more than 30 cancer types.
- Performed comprehensive genomic and clinical association analyses of disulfidptosis-related genes.
Main Results:
- FLNA and FLNB were the most frequently mutated genes; UCEC and SKCM showed highest mutation rates.
- Mutations in ACTN4 correlated with poorer survival in CESC and ESCA; breast cancer subtypes and KIRC showed potential disulfidptosis association.
- Disulfidptosis genes correlated with immune cell infiltration, EMT activation, and identified potential therapeutic compounds.
Conclusions:
- Disulfidptosis cell death genes are implicated in numerous cancer types.
- These genes hold promise as biomarkers for cancer diagnosis, prognosis, and therapy.
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