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Updated: Nov 15, 2025
Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
High VHL Expression Reverses Warburg Phenotype and Enhances Immunogenicity in Kidney Tumor Cells
Songbiao Zhu1, Wenxi Ding1, Yuling Chen1
1MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systematic Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Abstract:
Clear cell renal cell carcinoma (ccRCC) is a frequently occurring renal cancer. The Von Hippel-Lindau disease tumor suppressor VHL, a known tumor suppressor gene, is frequently mutated in about 50% of patients with ccRCC. However, it is unclear whether VHL influences the progression of ccRCC tumors expressing wild-type VHL. In the present study, we found that higher expression of VHL was correlated with the better disease-free survival (DFS) in ccRCC patients using The Cancer Genome Atlas (TCGA) datasets. We revealed that VHL overexpression in ccRCC cells inhibited epithelial-mesenchymal transition (EMT), sterol regulatory element-binding protein 1 (SREBP1)-regulated triglyceride synthesis, and cell proliferation. Proteomic analysis provided us a global view that VHL regulated four biological processes, including metabolism, immune regulation, apoptosis, and cell movement. Importantly, we found that VHL overexpression led to up-regulated expression of proteins associated with antigen processing and interferon-responsive proteins, thus rendering ccRCC cells more sensitive to interferon treatment. We defined an interferon-responsive signature (IRS) composed of ten interferon-responsive proteins, whose mRNA expression levels were positively correlated with DFS in ccRCC patients. Taken together, our results propose that the subset of ccRCC patients with high VHL expression benefit from immunotherapy.
Insights
Higher Von Hippel-Lindau (VHL) gene expression in clear cell renal cell carcinoma (ccRCC) correlates with better survival and improved response to interferon treatments. VHL may enhance immunotherapy benefits for ccRCC patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Clear cell renal cell carcinoma (ccRCC) is a common kidney cancer.
- The Von Hippel-Lindau (VHL) tumor suppressor gene is frequently mutated in ccRCC.
- The role of VHL in ccRCC tumors with wild-type VHL is not fully understood.
Purpose of the Study:
- To investigate the functional role of VHL in ccRCC progression and its impact on patient outcomes.
- To explore the molecular mechanisms by which VHL influences ccRCC biology.
- To identify potential therapeutic strategies for ccRCC based on VHL expression.
Main Methods:
- Analysis of The Cancer Genome Atlas (TCGA) datasets for VHL expression and disease-free survival (DFS).
- In vitro studies involving VHL overexpression in ccRCC cells.
- Proteomic analysis to identify VHL-regulated biological pathways.
- Development and validation of an interferon-responsive signature (IRS).
Main Results:
- Higher VHL expression is associated with improved DFS in ccRCC patients.
- VHL overexpression inhibits epithelial-mesenchymal transition (EMT), SREBP1-regulated triglyceride synthesis, and cell proliferation.
- VHL regulates key biological processes including metabolism, immune regulation, apoptosis, and cell movement.
- VHL overexpression up-regulates antigen processing and interferon-responsive proteins, increasing sensitivity to interferon treatment.
- An interferon-responsive signature (IRS) of ten proteins correlates positively with DFS.
Conclusions:
- VHL plays a significant role in ccRCC progression, independent of its mutation status.
- VHL overexpression confers sensitivity to interferon-based therapies.
- VHL expression levels can predict patient outcomes and guide immunotherapy decisions in ccRCC.
