Development and validation of a VHL-associated immune prognostic signature for clear cell renal cell carcinoma

BACKGROUND: VHL mutation is the most common mutation in clear cell renal cell carcinoma (ccRCC). Here, we developed and validated an immune-related signature to predict the prognosis of ccRCC with VHL mutations. METHODS: VHL mutation status and RNA expression were analysed in the TCGA datasets and our cohort. LASSO Cox analysis was performed to develop an immune-related signature. Candidate genes for the immune-related signature were differentially expressed between VHLwt and VHLmut ccRCC patients. RESULTS: VHL mutations resulted in the downregulation of the immune response in ccRCC. To develop an immune-related signature, LASSO Cox analysis was constructed by immune-related genes that were differentially expressed between VHLwt (WHL wild type) and VHLmut (VHL mutation) ccRCC patients. The signature was developed and validated in the TCGA and our own cohort to classify patients into groups based on having a low or high risk of poor survival. Functional enrichment analysis showed that the immune-related pathway represented the major function and pathway. In addition, patients in the high-risk group had a positive correlation with low fractions of CD4 + T cells and dendritic cells and presented a lower expression of CTLA-4 and PD-1 than the low-risk group. CONCLUSION: In this study, we proposed a novel immune-related signature, which is a feasible biomarker for predicting the overall survival in VHLmut patients with ccRCC.