Identification of a four immune-related genes signature based on an immunogenomic landscape analysis of clear cell renal cell carcinoma

J Cell Physiol. 2020 Dec;235(12):9834-9850. doi: 10.1002/jcp.29796. Epub 2020 May 26.


Renal clear cell carcinoma (ccRCC) is the most common type of renal cell carcinoma, which has strong immunogenicity. A comprehensive study of the role of immune-related genes (IRGs) in ccRCC is of great significance in finding ccRCC treatment targets and improving patient prognosis. In this study, we comprehensively analyzed the expression of IRGs in ccRCC based on The Cancer Genome Atlas datasets. The mechanism of differentially expressed IRGs in ccRCC was analyzed by bioinformatics. In addition, Cox regression analysis was used to screen prognostic related IRGs from differentially expressed IRGs. We also identified a four IRGs signature consisting of four IRGs (CXCL2, SEMA3G, PDGFD, and UCN) through lasso regression and multivariate Cox regression analysis. Further analysis results showed that the four IRGs signature could effectively predict the prognosis of patients with ccRCC, and its predictive power is independent of other clinical factors. In addition, the correlation analysis of immune cell infiltration showed that this four IRGs signature could effectively reflect the level of immune cell infiltration of ccRCC. We also found that the expression of immune checkpoint genes CTLA-4, LAG3, and PD-1 in the high-risk group was higher than that in the low-risk group. Our research revealed the role of IRGs in ccRCC, and developed a four IRGs signature that could be used to evaluate the prognosis of patients with ccRCC, which will help to develop personalized treatment strategies for patients with ccRCC and improve their prognosis. In addition, these four IRGs may be effective therapeutic targets for ccRCC.

Keywords: bioinformatics; clear cell renal cell carcinoma; immune-related genes; prognosis; therapeutic target.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / immunology
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / immunology*
  • Carcinoma, Renal Cell / pathology
  • Chemokine CXCL2 / genetics*
  • Chemokine CXCL2 / immunology
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic / immunology
  • Genome, Human / immunology
  • Humans
  • Immune Checkpoint Proteins / genetics
  • Immune Checkpoint Proteins / immunology
  • Immunogenetics
  • Lymphokines / genetics*
  • Lymphokines / immunology
  • Male
  • Middle Aged
  • Platelet-Derived Growth Factor / genetics*
  • Platelet-Derived Growth Factor / immunology
  • Prognosis
  • Proportional Hazards Models
  • Semaphorins / genetics*
  • Semaphorins / immunology
  • Transcriptome
  • Urocortins / genetics*
  • Urocortins / immunology


  • Biomarkers, Tumor
  • CXCL2 protein, human
  • Chemokine CXCL2
  • Immune Checkpoint Proteins
  • Lymphokines
  • PDGFD protein, human
  • Platelet-Derived Growth Factor
  • Semaphorins
  • UCN protein, human
  • Urocortins
  • semaphorin 3G, human