Comprehensive analysis of immune ferroptosis gene in renal clear cell carcinoma: prognosis and influence of tumor microenvironment.

Objective: We conducted an in-depth study of the immune system and ferroptosis to identify prognostic biomarkers and therapeutic targets for renal clear cell carcinoma.

Methods: Immune ferroptosis-related differentially expressed genes (IFR-DEGs) were selected from The Cancer Genome Atlas (TCGA). A lasso-Cox risk scoring model was established; its prognostic value was determined using prognostic analysis and single multivariate Cox analysis. Model genes were subjected to subcellular fluorescence localization, mRNA and protein expression analyses, and single-cell RNA sequencing localization analysis. Risk score was analyzed using the immune score, immune infiltrating cell correlation, immune checkpoint, TIDE, and drug sensitivity.

Results: A total of 103 IFR-DEGs were identified; a risk model comprising and was established. The survival curve, single multivariate Cox regression, and receiver operating characteristic (ROC) curve analysis showed that the model had good predictive ability (p < 0.05). It was also validated using the validation set and total cohort. Subcellular fluorescence localization revealed that ACADSB, CHAC1, and PLA2G6 were distributed in the cytoplasm and LURAP1L in the nucleus. The mRNA and protein expression trends were consistent. Single-cell RNA sequencing mapping revealed that ACADSB was enriched in distal tubule cell clusters. In the Kidney renal clear cell carcinoma (KIRC) mutation correlation analysis, 1.56% of the patients were found to have genetic alterations; The Spearman correlation analysis of model gene mutations showed that was positively correlated with , which may have a synergistic effect; it was negatively correlated with and , and was negatively correlated with , which may have an antagonistic effect. Model and immune correlation analyses found that high-risk patients had significantly higher levels of CD8+ T cells, regulatory T cells (Tregs), immune checkpoints, immune scores, and immune escape than those in low-risk patients. High-risk patients had a higher susceptibility to small-molecule drugs.

Conclusion: A novel prognostic model of immune ferroptosis-related genes ( and ), which plays an important role in immune infiltration, microenvironment, and immune escape, was constructed. It effectively predicts the survival of patients with KIRC.