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Updated: Jun 3, 2025
The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers
Published on: January 22, 2013
Sensitivity of renal cell carcinoma to cuproptosis: a bioinformatics analysis and experimental verification
Hongfang Li1, Chanjuan Zhang1, Neng Zhu2
1Laboratory of Stem Cell Regulation with Chinese Medicine and Its Application, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China.
Abstract:
Purpose: Targeting cuproptosis is considered as a promising therapeutic strategy for the prevention of tumors. However, the potential role of cuproptosis and its related genes in clear cell renal cell carcinoma (ccRCC) remains elusive. The present study aims to explore the sensitivity of ccRCC to cuproptosis and its underlying mechanism. Methods: Cuproptosis differential genes (CDGs) were extracted using the GSE53757 and GSE66272 datasets. A comprehensive analysis of the role of CDGs was conducted through multiple public databases and experiments. Results: It was found that cuproptosis inducer elesclomol significantly induced cell death in 786-O and A498 cells. FDX and DLAT exhibited significantly low expression, which were independent prognostic factors for poor survival, and had a strong positive correlation in ccRCC patients. Functional analysis of differentially expressed genes positively or negatively correlated with both FDX1 and DLAT indicated that acetyl-CoA biosynthetic process and acetyl-CoA metabolic process were remarkably affected. In ccRCC patients, the methylation levels and sites of FDX1 and DLAT genes were dramatically correlated with overall survival (OS). The expressions of FDX1 and DLAT were closely related to immune infiltration and immune checkpoints. Docking results indicated that mitotane, adicicol and dihydrolipoic acid might be potential drug targets for FDX1 and DLAT. Conclusions: Overall, the present study demonstrates the sensitivity of ccRCC to cuproptosis, and targeting the combination of FDX1 and DLAT may be a novel therapeutic strategy to induce cuproptosis in ccRCC.
Insights
Targeting cuproptosis, a cell death process, shows promise for clear cell renal cell carcinoma (ccRCC). Low expression of FDX1 and DLAT genes indicates poor survival and suggests a new therapeutic strategy for ccRCC.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Cuproptosis is an emerging therapeutic target for various cancers.
- The role of cuproptosis in clear cell renal cell carcinoma (ccRCC) is not well understood.
- Identifying novel therapeutic strategies for ccRCC is crucial.
Purpose of the Study:
- To investigate the sensitivity of ccRCC to cuproptosis.
- To explore the underlying molecular mechanisms of cuproptosis in ccRCC.
- To identify potential therapeutic targets for ccRCC treatment.
Main Methods:
- Differential gene expression analysis of cuproptosis-related genes using public datasets (GSE53757, GSE66272).
- In vitro experiments to assess the effect of cuproptosis inducers on ccRCC cell lines.
- Bioinformatic analysis including survival analysis, gene correlation, and pathway enrichment.
- Analysis of gene methylation, immune infiltration, and molecular docking.
Main Results:
- Elesclomol, a cuproptosis inducer, significantly reduced viability in ccRCC cell lines (786-O, A498).
- FDX1 and DLAT showed significantly low expression in ccRCC, correlating with poor prognosis and overall survival.
- Functional enrichment analysis highlighted the involvement of acetyl-CoA metabolic processes.
- FDX1 and DLAT expression correlated with immune infiltration and checkpoints; potential drug targets were identified.
Conclusions:
- ccRCC is sensitive to cuproptosis induction.
- Targeting the combination of FDX1 and DLAT presents a novel therapeutic strategy for ccRCC.
- Further research into FDX1 and DLAT as therapeutic targets could lead to new ccRCC treatments.
