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Development and validation of disulfidptosis-related genes signature for patients with glioma
Jia Wang1, Junchi Luo2, Sha Yang3
1Department of Neurosurgery, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing, China.
Background:
Disulfidptosis has recently emerged as a novel form of regulated cell death (RCD). Evasion of cell death is a hallmark of cancer, and the resistance of many tumors to apoptosis-inducing therapies has heightened interest in exploring alternative RCD mechanisms.
Methods:
Transcriptomic and clinical data were obtained from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Chinese Glioma Genome Atlas (CGGA). Glioma samples were classified using non-negative matrix factorization (NMF). A predictive model was constructed using Lasso regression analysis, and its performance was evaluated through receiver operating characteristic (ROC) and Kaplan-Meier survival analyses. The relationship between the model and the tumor immune microenvironment (TIME) as well as treatment sensitivity was also assessed. Finally, we validated the expression of key signature genes in glioma.
Results:
Glioma samples were categorized into two distinct subtypes based on disulfidptosis-related genes, showing significant differences in overall survival (OS) and progression-free survival (PFS) between the subtypes. A genetic risk score model was then developed using these genes. A nomogram predicting OS was constructed using the risk score and clinical variables. Patients were stratified into low- and high-risk groups based on the median risk score from the TCGA cohort. Low-risk patients had significantly better outcomes compared to high-risk patients (TCGA cohort, OS: p < 0.001; PFS: p < 0.001; CGGA cohort, OS: p < 0.001). The risk score was associated with HLA expression, immune checkpoint genes, immune cell infiltration, immune function, tumor mutation burden, tumor stemness score, and drug sensitivity. Lastly, the expression of 11 signature genes was confirmed in glioma tissues.
Conclusions:
The disulfidptosis-related gene-based risk score model effectively predicted glioma outcomes and highlighted the role of disulfidptosis-related genes in tumor immunity. This study offers potential new avenues for glioma treatment by targeting disulfidptosis.
Insights
This study introduces a novel risk score model based on disulfidptosis-related genes to predict glioma patient outcomes. The model also reveals connections between disulfidptosis, tumor immunity, and treatment sensitivity, offering new therapeutic strategies.
Area of Science:
- Oncology
- Cell Death Research
- Genomics
Background:
- Disulfidptosis is an emerging form of regulated cell death (RCD).
- Cancer cells evade cell death, driving interest in alternative RCDs like disulfidptosis.
- Tumor resistance to apoptosis necessitates exploring novel cell death pathways for cancer therapy.
Purpose of the Study:
- To investigate the role of disulfidptosis-related genes in glioma.
- To develop a predictive model for glioma prognosis based on disulfidptosis.
- To explore the relationship between disulfidptosis, tumor immunity, and treatment sensitivity in glioma.
Main Methods:
- Utilized transcriptomic and clinical data from TCGA, GTEx, and CGGA databases.
- Classified glioma samples and developed a predictive risk score model using Lasso regression.
- Evaluated model performance with ROC and Kaplan-Meier analyses; assessed associations with tumor immune microenvironment (TIME) and drug sensitivity.
Main Results:
- Identified two glioma subtypes based on disulfidptosis genes with significant survival differences.
- Developed a disulfidptosis-related gene risk score model and nomogram for predicting overall survival (OS) and progression-free survival (PFS).
- Risk score correlated with immune markers, cell infiltration, mutation burden, stemness, and drug sensitivity; validated key gene expression.
Conclusions:
- A disulfidptosis-related gene risk score model accurately predicts glioma patient outcomes.
- Disulfidptosis plays a significant role in glioma immunity.
- Targeting disulfidptosis presents a potential new therapeutic strategy for glioma.
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