Construction of an Immune-related Gene Model for Predicting Prognosis and Immune Infiltration in Clear Cell Renal Cell Carcinoma
Abstract Background: Clear cell renal cell carcinoma (ccRCC) is a common pathological type of kidney cancer with high immune infiltration that has been proven to be treatable with immune checkpoint inhibitor (ICI) therapy. However, the role of immunity in ccRCC remains poorly understood. Therefore, this paper aimed to develop and validate a novel immune-related prognostic marker to predict both the overall survival rate (OS) of ccRCC patients and the response to ICI therapy.Methods: Based on the transcriptome and clinicopathological data of ccRCC from The Cancer Genome Atlas (TCGA) dataset and immune-related genes (IRGs) from immune datasets, IRGs related to prognosis were screened to construct an IRG prognostic index (IRGPI) via coexpression analysis and Cox regression. After verifying that IRGPI was a prognostic indicator independent of clinical parameters, a nomogram was established. In addition, functional enrichment analysis, the CIBERSORT algorithm and single-sample gene set enrichment analysis (ssGSEA) were performed to compare the molecular and immune characteristics of IRGPI-defined subgroups. Finally, the expression of immunosuppressive genes, tumor mutational burden (TMB) and the TIDE algorithm were used to predict the response of ICI therapy in different IRGPI subgroups. Results: A total of 11 IRGs (IFNG, XCL1, APOBEC3G, CD86, CXCR3, IL10RA, IL2RG, CD244, SH2D1A, CD3D and FCER1G) were included in the IRGPI module. IRGPIhigh patients had a worse OS and had poorer clinical pathological status than IRGPIlow patients. A nomogram containing clinical features and IRGPI scores may guide the clinical practice of ccRCC. Chemokine signaling pathways were mainly involved in functional enrichment analysis. Furthermore, the IRGPI could effectively reflect the immune characteristics and immune checkpoint gene expression of ccRCC and the response to ICI therapy.Conclusions: The IRGPI is a promising biomarker for determining prognosis and has the potential to be used to predict immunotherapy response in ccRCC.