Development and validation of an immune prognostic classifier for clear cell renal cell carcinoma

Cancer Biomark. 2020;27(2):265-275. doi: 10.3233/CBM-191017.

Abstract

Background: Tumor-infiltrating immune cells are indispensable to the progression and prognosis of clear cell renal cell carcinoma (ccRCC).

Objective: The aim of this study was to explore the clinical implications of immune cell infiltrates in ccRCC.

Methods: The Cancer Genome Atlas (TCGA) database (N= 515) and E-MTAB-1980 cohort of patients (N= 101) were adopted to estimate the prognostic value of immune cell infiltration. Twenty-four types of immune cells were evaluated using single-sample gene set enrichment analysis. Cox regression analyses were conducted to develop an immune risk score.

Results: Survival analyses revealed that 13 genes significantly associated with the overall survival (OS). Furthermore, multivariate Cox analysis identified an immune risk score on the basis of mast cells, natural killer CD56bright cells, T helper 17 (Th17) cells, and Th2 cells. The immune risk score was associated with OS, with hazard ratios of 2.72 (95% CI 2.17-3.40) and 3.24 (95% CI 1.64-6.44) in TCGA and E-MTAB-1980 datasets, respectively. This immune risk score was significantly correlated with some immunotherapy-related biomarkers.

Conclusions: We profiled a prognostic signature and established an immune risk score model for ccRCC, which could provide novel predictive markers for patients with ccRCC and an indicator for immunotherapy response measurement.

Keywords: Clear cell renal cell carcinoma; RNA-sequencing; prognosis; tumor-infiltrating immune cells.

Publication types

  • Validation Study

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / immunology
  • Carcinoma, Renal Cell / classification
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / immunology*
  • Carcinoma, Renal Cell / pathology
  • Cohort Studies
  • Female
  • Gene Expression Profiling
  • Humans
  • Kidney Neoplasms / classification
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / immunology*
  • Kidney Neoplasms / pathology
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Male
  • Middle Aged
  • Prognosis
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / immunology
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • RNA, Neoplasm