Gene expression-based immune infiltration analyses of renal cancer and their associations with survival outcome

Abstract

Background: Renal cancer is a common malignant tumor with an increasing incidence rate.

Methods: In this study, based on the gene expression profiles, we analyzed the compositions of tumor-infiltrating immune cells (TIICs) in renal cancer and paracancerous samples using CIBERSORT. The proportions of 22 TIICs subsets in 122 paired renal carcinoma and paracancerous samples, and 224 Wilms tumor (WT) samples varied between intragroup and intergroup.

Results: After analyzed the difference of TIICs composition between renal cancer and paired paracancerous samples, we found that M0 macrophages and CD8 T cells were significantly elevated, while naive B cells were significantly decreased in renal cancer samples compared with paracancerous samples. Survival analysis showed that high overall TIICs proportion, the low proportion of resting mast cells and the high proportion of activated memory CD4 T cells were associated with poor prognosis of renal cancer patients. In addition, 3 clusters were identified by hierarchical clustering analysis, and they presented a distinct prognosis. Cluster 1 had superior survival outcomes, while cluster 2 had an inferior survival outcome.

Conclusions: Our study indicated that overall TIICs proportion, certain TIICs subset proportion, including resting mast cells and activated memory CD4 T cells, and distinct cluster patterns were associated with the prognosis of renal cancer, which was significant for the clinical surveillance and treatment of renal cancer.

Keywords: Prognosis; Proportion; Renal cancer; Tumor-infiltrating immune cells.

Fig. 1

Renal cancer samples from GEO and TCGA had highly consistent immune cell proportion. a TIICs compositions of renal cancer and paracancerous samples from TCGA and GEO analyzed by CIBERSORT. b Proportions of TIICs subsets in renal cancer samples from TCGA and GEO

Fig. 2

Obvious intragroup and intergroup differences in TIICs fraction were observed among paired renal cancer and paracancerous samples from TCGA, and WT samples from GEO. a Immune infiltration in paired paracancerous samples. b Immune infiltration in paired renal cancer samples. c Immune infiltration in WT samples. d Volcano plot of TIICs subsets proportions between paired renal cancer and paracancerous samples. Compared with paired paracancerous samples, M0 macrophages and CD8 T cells were significantly elevated, while naive B cells were significantly decreased in renal cancer samples

Fig. 3

P-value of CIBERSORT represented the overall proportion of TIICs. a Proportions of samples with P-value < 0.05 and P-value ≥0.05 in GEO and TCGA datasets. b Immune cytolytic activity of samples with P-value < 0.05 and P-value ≥0.05 in TCGA and GEO cohort. c Survival curves of samples stratified by P-value of 0.05. Compared with renal cancer patients with P-value ≥0.05, patients with P-value < 0.05 had poor survival outcome (p < 0.0001)

Fig. 4

Decreased resting mast cells and elevated activated memory CD4 T cells were associated with poor prognosis of renal cancer patients. a Association of 22 TIICs subsets with survival outcomes of renal cancer patients. * and ** indicated statistical significance. b Survival curve of resting mast cells stratified by median proportion. c Survival curve of activated memory CD4 T cells stratified by median proportion

Fig. 5

Immune clusters were associated with the prognosis of renal cancer patients. a Euclidean distance model identified three different immune clusters (cluster 1, cluster 2 and cluster 3). b Survival curves of cluster 1, 2 and 3. Cluster 1 presented superior survival outcomes, while cluster 2 presented inferior survival outcomes (p = 0.0057). c The 3 clusters exhibited different compositions of 22 TIICs subsets