Classification of renal cell carcinoma based on immunogenomic profiling

Renal cell carcinoma (RCC) is the most common type of kidney cancer. Several studies have identified RCC subtypes based on genomic profiling. However, few studies have explored the stratification of RCC based on immune-associated gene sets, which may contribute to the optimal classification of patients with RCC who respond to immunotherapy. By analyzing the molecular and clinical data of RCC obtained from The Cancer Genome Atlas database, we classified RCC hierarchically based on the scores of 29 immune-associated gene sets, which were generated by single-sample gene-set enrichment analysis. The three RCC subtypes were Cluster1 (C1), Cluster2 (C2) and Cluster3 (C3), and they had distinct prognoses. The C1 subtype was associated with worse survival than the others, but the prognoses of the C2 and C3 subtypes were not significantly different. The three RCC subtypes also had distinct DNA damage markers, key immune characteristics, proportions of tumor-infiltrating immune cells, and gene expressions of immunomodulators. In addition to the immune-related pathways, some cancer-associated pathways were also overactivated for the C1 subtype, these included apoptosis and the PI3K-Akt signaling pathway. Finally, this study showed that immune signature-based classification has potential clinical implications for RCC treatment.