Analyzing and validating the prognostic value and immune microenvironment of clear cell renal cell carcinoma

Abstract

ABSTRACT Tumor immune microenvironment (TIME) plays an important role in tumor diagnosis, prevention, treatment and prognosis. However, the correlation and potential mechanism between clear cell renal cell carcinoma (ccRCC) and its TIME are not clear. Therefore, we aimed to identify potential prognostic biomarkers related to TIME of ccRCC. 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. 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. WGCNA revealed that the red module has an important relationship with TIME, and obtained 14 hub genes. In addition, the nomogram containing LAG3 and GZMK accurately predicted OS outcomes of ccRCC patients. LAG3 and GZMK have a certain correlation with the prognosis of ccRCC patients, and play an important role in the TIME. These two hub genes deserve further study as biomarkers of the TIME.