Abstract

Kidney cancer encompasses a range of primary cancers, such as clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC). Our knowledge about the tumor microenvironment (TME) of kidney cancer is still limited. Therefore, we comprehensively assessed the TME of kidney cancers (including ccRCC and pRCC) using the ESTIAMTE, and CIBERSORT algorithms, and conducted distinct functional and correlation analyses with data from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), Gene Expression Omnibus (GEO), Connectivity map and CellMiner database. Next, we identified two immune-related hub genes, IGLL5 and IL2RA, which play essential roles in the TME as well as on survival in ccRCC and pRCC. Furthermore, ccRCC and pRCC samples from our medical center were collected to verify the clinical application value of these two immune-related genes. A specific enrichment analysis of immune cells related to IGLL5 and IL2RA was also conducted in two types of renal cell cancer. Based on selected genes, we predicted the drug response and uncovered novel drug candidate for RCC treatment. Considering the unfavorable outcomes of kidney cancer and emerging interest in TME-targeted treatments, our results may offer insights into immune-related molecular mechanisms and possible targets to control the kidney cancer.

Highlights

  • Kidney or renal cancer is the sixth most common malignant cancer in men and the ninth most common in women

  • We first determined the association between ESTIMATE scores, prognosis as well as clinical characteristics in clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC)

  • CcRCC and pRCC are the main subtypes with high incidence and high mortality (Comprehensive molecular c, 2013; Chen et al, 2016; Linehan et al, 2016; Hsieh et al, 2017)

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Summary

Introduction

Kidney or renal cancer is the sixth most common malignant cancer in men and the ninth most common in women. TME, as an integral part of tumors, is a cellular environment consisting of tumor cells and other non-malignant cells, including surrounding immune cells, lymphocytes, fibroblasts, stromal cells, and blood vessels (Wu and Dai, 2017). A wealth of new information has emerged which reveals how the functionality of TME determines its integral and indispensable role in various cancers (Hanahan and Coussens, 2012; Pitt et al, 2016). Within the TME, various types of immune and nonimmune cell are found. Some nontumor cells, such as stromal cells, fibroblasts, may accelerate cancer cell proliferation and stimulate cancer progression (Hanahan and Coussens, 2012). Cancer cells are able to adapt and grow with less possibility of detection and eradication by immunosurveillance

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