Single-Cell RNA-Seq Analysis Reveals Ferroptosis in the Tumor Microenvironment of Clear Cell Renal Cell Carcinoma

Abstract

In this study, we investigated the role of ferroptosis in the tumor microenvironment (TME) of clear cell renal cell carcinoma (ccRCC), the leading cause of renal cancer-related death. We analyzed single-cell data from seven ccRCC cases to determine cell types most correlated with ferroptosis and performed pseudotime analysis on three myeloid subtypes. We identified 16 immune-related ferroptosis genes (IRFGs) by analyzing differentially expressed genes between cell subgroups and between high and low immune infiltration groups in the TCGA-KIRC dataset and the FerrDb V2 database. Using univariate and multivariate Cox regression, we identified two independent prognostic genes, AMN and PDK4, and constructed an IRFG score model immune-related ferroptosis genes risk score (IRFGRs) to evaluate its prognostic value in ccRCC. The IRFGRs demonstrated excellent and stable performance for predicting ccRCC patient survival in both the TCGA training set and the ArrayExpress validation set, with an AUC range of 0.690–0.754, outperforming other commonly used clinicopathological indicators. Our findings enhance the understanding of TME infiltration with ferroptosis and identify immune-mediated ferroptosis genes associated with prognosis in ccRCC.