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Updated: Oct 8, 2025
The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers
Published on: January 22, 2013
Differentially Expressed Genes in Clear Cell Renal Cell Carcinoma as a Potential Marker for Prognostic and Immune
Ying Tong1, Yiwen Yu1, Hui Zheng1
1Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China.
Abstract:
Clear cell renal cell carcinoma (ccRCC) is characterized by the inactivation of the von Hippel-Lindau (VHL) gene. Of note, no other gene is mutated as frequently as VHL in ccRCC, turning out that patients with inactivated VHL constitute the majority of ccRCC-related character. Thus, differentially expressed genes (DEGs) and their molecular networks caused by VHL mutation were considered as important factors for influencing the prognosis of ccRCC. Here, we first screened out six DEGs (GSTA1, GSTA2, NAT8, FABP7, SLC17A3, and SLC17A4) which downregulated in ccRCC patients with VHL non-mutation than with the mutation. Generally, most DEGs with high expression were associated with a favorable prognosis and low-risk score. Meanwhile, we spotted transcription factors and their kinases as hubs of DEGs. Finally, we clustered ccRCC patients into three subgroups according to the expression of hub proteins, and analyzed these subgroups with clinical profile, outcome, immune infiltration, and potential Immune checkpoint blockade (ICB) response. Herein, DEGs might be a promising biomarker panel for immunotherapy and prognosis in ccRCC. Moreover, the ccRCC subtype associated with high expression of hubs fit better for ICB therapy.
Insights
Clear cell renal cell carcinoma (ccRCC) prognosis is linked to von Hippel-Lindau (VHL) gene mutations. Differentially expressed genes (DEGs) associated with VHL status may serve as biomarkers for ccRCC immunotherapy and patient outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Clear cell renal cell carcinoma (ccRCC) is strongly associated with von Hippel-Lindau (VHL) gene inactivation, affecting the majority of patients.
- VHL gene mutations significantly influence the molecular landscape and prognosis of ccRCC.
Purpose of the Study:
- To identify differentially expressed genes (DEGs) and their associated molecular networks in ccRCC related to VHL gene status.
- To explore the prognostic and predictive value of these DEGs and their regulatory networks in ccRCC, particularly for immunotherapy response.
Main Methods:
- Screening of six downregulated DEGs (GSTA1, GSTA2, NAT8, FABP7, SLC17A3, SLC17A4) in ccRCC patients with VHL non-mutation compared to VHL-mutated patients.
- Identification of transcription factors and kinases as key regulatory hubs within the DEG networks.
- Clustering of ccRCC patients into three subgroups based on hub protein expression and subsequent analysis of clinical profiles, outcomes, immune infiltration, and potential response to immune checkpoint blockade (ICB).
Main Results:
- Most identified DEGs with high expression correlated with favorable prognoses and lower-risk scores in ccRCC.
- Transcription factors and kinases were identified as central hubs regulating the expression of these DEGs.
- Patient subgroups exhibited distinct clinical characteristics, prognoses, and immune infiltration patterns, with one subgroup showing better response to ICB therapy.
Conclusions:
- Differentially expressed genes (DEGs) associated with VHL status represent a potential biomarker panel for ccRCC prognosis and immunotherapy.
- The identified ccRCC subtype characterized by high hub protein expression demonstrates enhanced suitability for ICB therapy.
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