High VHL Expression Reverses Warburg Phenotype and Enhances Immunogenicity in Kidney Tumor Cells
- Author:
Zhu SONGBIAO
1
;
Ding WENXI
;
Chen YULING
;
Wang WEIXUAN
;
Xu RENHUA
;
Liu CHONGDONG
;
Liu XIAOHUI
;
Deng HAITENG
Author Information
1. MOE Key Laboratory of Bioinformatics,Center for Synthetic and Systematic Biology,School of Life Sciences,Tsinghua University,Beijing 100084,China
- Keywords:
Renal cancer;
VHL;
Immunogenicity;
Multi-omics;
Interferon
- From:
Genomics, Proteomics & Bioinformatics
2022;20(4):657-669
- CountryChina
- Language:Chinese
-
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 anal-ysis 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.
