Abstract
Background: To explore the hub genes related with prognostic pathway based on tumor microenvironment (TME) in clear cell renal cell carcinoma (ccRCC), a prognostic risk signature was identified to evaluate ccRCC patients’ prognosis.
Methods: The immune scores of ccRCC patients were calculated via “ESTIMATE” package. The hub genes of the key pathway were selected using univariate cox and Lasso regression analysis. Cluster analysis and risk signature construction were performed in accordance with the expression levels and lasso coefficient of the hub genes.
Results:Cytokine/cytokine receptor intersection pathway was considered as a key prognostic pathway in ccRCC. 6 differentially expressed cytokine/cytokine receptor pathway-related genes (DECCRGs) (CCR10, CXCL5, IL20RB, INHBE, KDR and RELT) were subsequently selected. Results of the cluster analysis revealed that the overall survival (OS) of the patients in cluster1 was better. Then, a 6-DECCRG immune-prognostic risk signature was established and used to evaluate the OS of ccRCC patients. This risk signature exhibited a good prognostic prediction ability in TCGA training cohort, which was further confirmed in TCGA testing cohort, whole cohort, GSE22541 cohort and a local cohort. Notably, the cluster groups and risk scores had a close connection to immune infiltration levels, respectively. CCR10, one of 6 DECCRGs, was further validated in renal cancer cells. Interestingly, reduced CCR10resulted in the inhibition of proliferation and migration in renal cancer cells.
Conclusion: Collectively, a novel 6-DECCRG immune-prognostic risk signature contributes to the accurate prediction of ccRCC prognosis.