Exploration of immune-related genes in high and low tumor mutation burden groups of chromophobe renal cell carcinoma.

Lei Li,Qing Zhou,Haosheng Liu,Lu Hao,Qiuyan Chen,Xi Chen

doi:10.1042/bsr20201491

Abstract

Renal cell carcinoma (RCC) is one of most common cancers with gradually increasing incidence and high mortality. Chromogenic RCC (chRCC) is the third most common histological subtype of RCC, accounting for approximately 5–7% of RCC. In our study, the transcriptome expression profile data (n=89) of chRCC, corresponding clinical data (n=113) and the somatic mutation data (n=66) were obtained from the TCGA database. We first analyzed the mutation data of chRCC patients and divided chRCC patients into high and low tumor mutation burden (TMB) groups based on the median TMB. We found that high TMB was significantly associated with worse prognosis and could promote tumor metastasis and development. Moreover, four different immune-related genes (BIRC5, PDGFRL, INHBE, IL20RB) were also identified. We found that BIRC5 was significantly overexpressed in the high TMB group and correlated with worse prognosis. The results of univariate and multivariate COX analyses demonstrated that BIRC5 (hazard ratio (HR) = 2.094) may serve as a prognostic indicator for patients with chRCC with high TMB. In addition, we identified the possible functional pathways of BIRC5 through gene set enrichment analysis (GSEA) enrichment. A positive correlation was obtained between BIRC5 and the abundance of CD4+ T cells. The results of our study revealed their correlation between the immune-related genes and clinicopathologic features as well as potential functional pathways as well as immune infiltrating cells, which may provide more data about the development of chRCC immunotherapy.

Highlights

Kidney cancer is well known as the third most common malignant tumor in the urinary system after prostate cancer and bladder cancer [1,2,3]
tumor mutation burden (TMB) is defined as the total number of mutations per megabase in tumor tissue. ‘maftools’ R package was used to calculate the mutations of each sample in chromogenic renal cell carcinoma (RCC) (chRCC), and all the chRCC samples were divided into low and high TMB groups based on median data
We found that BIRC5, PDGFRL, INHBE, and IL20RB were highly expressed in the high TMB group (Figure 3B–E)

Summary

Introduction

Kidney cancer is well known as the third most common malignant tumor in the urinary system after prostate cancer and bladder cancer [1,2,3]. 90% of kidney cancers are renal cell carcinoma (RCC), including clear cell RCC (ccRCC), chromogenic RCC (chRCC) and papillary RCC (pRCC). ChRCC is the third most common histological subtype of RCC, accounting for approximately 5–7% of RCC [5,6,7]. There are many treatments for chRCC, but immunotherapy is considered to be the most promising and immune checkpoint inhibitor proven useful for RCC [8,9]. The role of immunotherapy in chRCC is far from fully clarified

Methods

Results

Conclusion