As a Newly-Discovered Component in Tumor Microenvironment RUFY4 Participates in Regulation of T cell via Cytokine-Interaction and Predicts Prognosis and Immunotherapy Responsiveness of Clear Cell Renal Carcinoma Patients

Abstract Background: clear cell renal cell carcinoma (ccRCC) is one of the most lethal kinds of malignancies in urinary system and the existing immunotherapy have not achieved satisfactory outcomes. Therefore, this study aims to establish a brand-new gene signature for immune-infiltration and clinical outcome (overall survival and immunotherapy responsiveness) of patients with ccRCC. Methods: Based on RNA sequencing data and clinical information in the Cancer Genome Atlas Project (TCGA) database, we investigated proportions of immune cells in 611 samples by an online tool CIBERSORTx. Multivariate survival analysis was used to determine crucial survival-associated immune cells and immune-infiltration-related genes (IIRGs). Next ROC analysis was carried on to evaluate the ability of IIRGs to distinguish patients and functional enrichment analysis were implemented to explore potential interaction network between immune cells and IIRGs. Results: T cells follicular helper (TFHs) and T cells regulatory (Tregs) were highly infiltrated in the tumor microenvironment and their abundance ratios were independent prognostic factors for overall survival. Among IIRGs of TFHs and TREGs, RUFY4 was found to be highly activated in tumor microenvironment and its co-expression network was enriched in regulation of T cells via cytokine-cytokine receptor interactions.Conclusion: These two cells and RUFY4, considered prognostic biomarkers and immunotherapeutic predictors of ccRCC patients, might also simultaneously affect the regulatory network in tumor microenvironment (TME) through cytokine interactions.