TNFSF13B and PPARGC1A expression is associated with tumor-infiltrating immune cell abundance and prognosis in clear cell renal cell carcinoma

Growing evidence suggests that the tumor microenvironment (TME) plays crucial roles in tumor progression and treatment efficacy in clear cell renal cell carcinoma (ccRCC), which typically has a poor prognosis due to high relapse and metastasis rates. We comprehensively analyzed ccRCC RNA-sequencing data from The Cancer Genome Atlas (TCGA) database to identify candidate prognostic TME-related genes involved in ccRCC. We used the ESTIMATE and CIBERSORT algorithms to estimate the proportions of immune cells, stromal cells, and tumor-infiltrating immune cells (TICs) in the TME in ccRCC samples from 539 patients. By examining the intersection of the differentially expressed genes (DEGs) obtained by Cox regression analysis and protein-protein interaction network, we identified five overlapping DEGs (IGLL5, MZB1, HSD11B1, TNFSF13B, and PPARGC1A). Further analysis revealed that TNFSF13B expression was elevated in ccRCC tumor tissues and negatively associated with overall survival. PPARGC1A expression exhibited the opposite patterns. Immunohistochemical analysis of 35 paired ccRCC and adjacent normal tissues confirmed the in-silico results. Gene set enrichment analysis revealed that genes in the groups with high TNFSF13B and PPARGC1A expression were enriched mainly in immune-related activities. In the group with low PPARGC1A expression, genes were enriched in metabolic pathways. CIBERSORT analysis of TIC proportions revealed that Tregs and CD8 T-cell abundance correlated positively with TNFSF13B expression, but negatively with PPARGC1A expression. These findings demonstrate that TNFSF13B and PPARGC1A are prognostic predictors and possible therapeutic targets in ccRCC.