Analyzing and validating the prognostic value and immune microenvironment of clear cell renal cell carcinoma
Abstract Background: There is still controversy regarding immunotherapy biomarkers. Therefore, we aimed to identify prognostic biomarkers related to immunotherapy for clear cell renal cell carcinoma (ccRCC).Methods: Fragments Per Kilobase Million (FPKM) data and clinical characteristics for ccRCC patients from The Cancer Genome Atlas (TCGA) database were downloaded. Unsupervised consensus clustering analysis was performed to divide patients into different immune subgroups according to their single-sample gene set enrichment analysis (ssGSEA) scores. Then, we validated the differences in immune cell infiltration, prognosis, clinical characteristics and expression levels of HLA and immune checkpoint genes between different immune subgroups. Weighted gene coexpression network analysis (WGCNA) was used to identify the significant modules and hub genes that were related to the immune subgroups. A nomogram was established to predict the overall survival (OS) outcomes after independent prognostic factors were identified by least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analyses.Results: Five clusters (immune subgroups) were identified. There was no significant difference in age, sex or N stage. And there were significant differences in race, T stage, M stage, grade, prognosis and tumor microenvironment. HLA gene families and CTLA4 showed significant differences between the five clusters, while PD1 and PDL1 did not. The red module was significant, and 14 hub genes were obtained. In addition, the nomogram containing LAG3 and GZMK accurately predicted OS outcomes of ccRCC patients.Conclusion: LAG3 and GZMK are strongly related to immunity and may provide suggestions for ccRCC immunotherapy.