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FOXP3 as a prognostic marker and therapeutic target in immunogenic cell death modulation for clear cell renal cell
Jian Chen1, Cheng Zhu1, Yan He1
1Medical Department, Ningbo Women and Children's Hospital, Ningbo, Zhejiang, China.
Background:
Clear cell renal cell carcinoma (ccRCC) remains a challenging cancer type due to its resistance to standard treatments. Immunogenic cell death (ICD) has the potential to activate anti-tumor immunity, presenting a promising avenue for ccRCC therapies.
Methods:
We analyzed data from GSE29609, TCGA-KIRC, and GSE159115 to identify ICD-related prognostic genes in ccRCC. By applying consensus clustering, patients were categorized based on ICD modification patterns, and an ICD signature (ICDS) model was developed using a PCA approach. Functional studies were conducted with FOXP3 knockdown in ccRCC cell lines to explore its impact on cell behavior.
Results:
Eleven ICD-related genes were identified as key prognostic indicators in ccRCC, with high ICDS linked to worse survival outcomes. High ICDS also correlated with increased levels of immune-suppressive cells within the tumor microenvironment. FOXP3 was highlighted as a critical gene influencing ICD, where its knockdown significantly reduced ccRCC cell proliferation and migration, underscoring its role in tumor progression.
Conclusions:
This study establishes FOXP3 as a pivotal factor in ICD regulation and ccRCC progression. Targeting FOXP3 and other ICD pathways could enhance treatment efficacy in ccRCC, providing a foundation for ICD-based therapeutic strategies. Evaluating ICD patterns in ccRCC may guide patient-specific interventions, paving the way for improved management of this aggressive cancer.
Insights
This study identifies key genes related to immunogenic cell death (ICD) in clear cell renal cell carcinoma (ccRCC). Targeting FOXP3, a critical gene in ICD, shows potential for improving ccRCC treatment efficacy.
Area of Science:
- Oncology
- Immunology
- Cancer Genomics
Background:
- Clear cell renal cell carcinoma (ccRCC) exhibits resistance to conventional therapies.
- Immunogenic cell death (ICD) offers a promising strategy to stimulate anti-tumor immunity in ccRCC.
Purpose of the Study:
- To identify prognostic genes associated with ICD in ccRCC.
- To develop an ICD signature (ICDS) model for patient stratification.
- To investigate the role of FOXP3 in ccRCC progression and ICD.
Main Methods:
- Analysis of multi-cohort ccRCC gene expression data (GSE29609, TCGA-KIRC, GSE159115).
- Consensus clustering to define patient subgroups based on ICD patterns.
- Principal Component Analysis (PCA) for ICDS model development.
- Functional assays involving FOXP3 knockdown in ccRCC cell lines.
Main Results:
- Eleven ICD-related genes were identified as significant prognostic markers for ccRCC.
- A high ICDS score correlated with poorer patient survival and an immunosuppressive tumor microenvironment.
- FOXP3 knockdown suppressed ccRCC cell proliferation and migration, highlighting its oncogenic role.
Conclusions:
- FOXP3 is a key regulator of ICD and ccRCC progression.
- Targeting FOXP3 and ICD pathways may enhance ccRCC treatment outcomes.
- Assessing ICD patterns can inform personalized ccRCC therapeutic strategies.
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