Abstract
Immune status affects the initiation and progression of clear cell renal cell carcinoma (ccRCC), the most common subtype of renal cell carcinoma. In this study, we identified an immune-related, five-gene signature that improves survival prediction in ccRCC. Patients were classified as high- and low-risk based on the signature risk score. Survival analysis showed differential prognosis, while principal component analysis revealed distinctly different immune phenotypes between the two risk groups. High-risk patients tended to have advanced stage, higher grade disease, and poorer prognoses. Functional enrichment analysis showed that the signature genes were mainly involved in the cytokine-cytokine receptor interaction pathway. Moreover, we found that tumors from high-risk patients had higher relative abundance of T follicular helper cells, regulatory T cells, and M0 macrophages, and higher expression of PD-1, CTLA-4, LAG3, and CD47 than low-risk patients. This suggests our gene signature may not only serve as an indicator of tumor immune status, but may be a promising tool to select high-risk patients who may benefit from immune checkpoint inhibitor therapy. Multivariate Cox regression analysis showed that the signature remained an independent prognostic factor after adjusting for clinicopathological variables, while prognostic accuracy was further improved after integrating clinical parameters into the analysis.
Highlights
Clear cell renal cell carcinoma is the most common subtype of renal cell carcinoma (RCC), accounting for approximately 80% to 90% of cases [1]
From 72 paired specimens in The Cancer Genome Atlas (TCGA), we further identified 4,629 differently expressed genes (DEGs), including 2,174 up-regulated and 2,455 downregulated transcripts
Protein Analysis Through Evolutionary Relationships (PANTHER) pathway analysis revealed that immune-related pathways, such as interleukin signaling pathway, inflammation mediated by chemokine and cytokine signaling pathway, B cell activation, and T cell activation, were associated with these differentially expressed immune-related genes (IRGs) (Supplementary Table 3)
Summary
Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma (RCC), accounting for approximately 80% to 90% of cases [1]. CcRCC has more malignant characteristics and worse prognosis, and is responsible for most RCCrelated deaths [2]. According to the latest global cancer statistics released in 2018, each year approximately 403,000 people are diagnosed with RCC and 175,000 patients die from the disease [3]. Patients with RCC typically undergo surgical treatment, and improved surgical methods have contributed to favorable overall prognosis [4]. Uncontrolled tumor progression and death will still occur in approximately 30% of RCC patients despite initial curative surgery [2]. More effective systemic treatments for RCC patients are needed to improve outcomes
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