Comprehensive Genomic Characterization of Tumor Microenvironment and Relevant Signature in Clear Cell Renal Cell Carcinoma

PURPOSE: To systematically investigate the characterization of tumor microenvironment (TME) in clear cell renal cell carcinoma (ccRCC), we performed a comprehensive analysis incorporating genomic alterations, cellular interactions, infiltrating immune cells, and risk signature. PATIENTS AND METHODS: Multi-omics data including RNA-seq, single-nucleotide variant (SNV) data, copy number variation (CNV) data, miRNA, and corresponding prognostic data were obtained from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) database. The CIBERSORT algorithm was utilized to identify prognostic TME subclusters, and TMEscore was further quantified. Moreover, the mutational landscape of TCGA-KIRC was explored. Lastly, TIDE resource was applied to assess the significance of TMEscore in predicting immunotherapeutic benefits. RESULTS: We analyzed the TME infiltration patterns from 621 ccRCC patients and identified 5 specific TME subclusters associated with clinical outcomes. Then, we found that TMEcluster5 was significantly related to favorable prognosis and enriched memory B-cell infiltration. Accordingly, we depicted the clustering landscape of TMEclusters, TMEscore levels, tumor mutation burden (TMB), tumor grades, purity, and ploidy in all patients. Lastly, TIDE was used to assess the efficiency of immune checkpoint blockers (ICBs) and found that the TMEscore has superior predictive significance to TMB, making it an essential independent prognostic biomarker and drug indicator for clinical use. CONCLUSIONS: Our study depicted the clustering landscape of TMEclusters, TMEscore levels, TMB, tumor grades, purity, and ploidy in total ccRCC patients. The TMEscore was proved to have promising significance for predicting prognosis and ICB responses, in accordance with the goal of developing rationally individualized therapeutic interventions.