Comprehensive insights on pivotal prognostic signature involved in clear cell renal cell carcinoma microenvironment using the ESTIMATE algorithm

Abstract

Emerging evidence has highlighted that the immune and stromal cells formed the majority of tumor microenvironment (TME) which are served as important roles in tumor progression. In our study, we aimed to screen vital prognostic signature associated with TME in clear cell renal cell carcinoma (ccRCC). We obtained total 611 samples from TCGA database consisting of transcriptome profiles and clinical data. ESTIMATE algorithm was applied to estimate the infiltrating fractions of immune/stromal cells. We found that the immune scores revealed more prognostic significance in overall survival and positive associations with risk clinical factors than stromal scores. We carried out differential expression analysis between Immunescore and stromalscore groups to obtain the 72 intersect genes. Protein to protein interaction (PPI) network and functional analysis was performed to indicate potential altered pathways. Additionally, we further conducted multivariate Cox analysis to identify 12 hub genes associated highly with TME of ccRCC using a stepwise regression procedure. Accordingly, risk score was constructed from the multivariate Cox results and Receiver Operating Characteristic (ROC) curve was used to assess the predictive value (AUC = 0.781). The ccRCC patients with high risk scores suffered poor survival outcomes than that with low risk scores. In the validation cohort from GSE53757, TNFSF13B, CASP5, and GJB6 correlated positively with tumor stages, while FREM1 negatively correlated with tumor stages. Importantly, we further observed that TNFSF13B, CASP5 and XCR1 showed the remarkable correlations with tumor-infiltrating immune cells. Taken together, our research identified specific signatures that related to the infiltration of stromal and immune cells in TME of ccRCC using the transciptome profiles, which reached a comprehensive understanding of tumor microenvironment in ccRCC.