Development and validation of a VHL-associated immune prognostic signature for clear cell renal cell carcinoma
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Cancer Cell International Open Access
PRIMARY RESEARCH
Development and validation of a VHL‑associated immune prognostic signature for clear cell renal cell carcinoma Jin Zhang2†, Aiting Yan3†, Wei Cao1†, Honglei Shi1, Kai Cao1,2 and Xiaowu Liu1*
Abstract 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 immunerelated 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. Keywords: Clear cell renal cell carcinoma (ccRCC), VHL mutation, Tumour-infiltrating Background Renal cell carcinoma (RCC) is the second most common malignancy in the urinary system and accounts for more than 90% of kidney malignancies [1]. In the United States, a total of 73,750 new cancer cases and 14,830 deaths from kidney and renal pelvis cancers were estimated in 2020 [2]. Clear cell renal cell carcinoma (ccRCC) is the
*Correspondence: [email protected] † Jin Zhang, Aiting Yan and Wei Cao contribute equally to this work 1 Department of Urology Surgery, Changzhou Wujin People’s Hospital, Wujin Hospital Affiliated Jiangsu University, The Wujin Clinical College of Xuzhou Medical University, Yongning north road 2, Tianning, Changzhou 213000, People’s Republic of China Full list of author information is available at the end of the article
most common histologic subtype of RCC based on pathologic classification, which accounts for approximately 70% of all RCC cases [3]. The carcinogenesis of ccRCC is a complex process mediated by various drivers and environmental risk factors, such as obesity and smoking [3]. Recently, immune checkpoint inhibitors (ICIs), such as anti-PD-1/PD-L1 inhibitors, have emerged as a significant therapeutic approach for advanced and metastatic ccRCC [4]. However, only a fraction of patients benefit from treatment w
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