Comprehensive analysis of immune ferropotosis gene on renal clear cell carcinoma: Prognosis and influence of tumor microenvironment

Abstract In this study, immune-ferropotosis-related prognostic differentially expressed genes (IFR-DEGs) were selected from the TCGA database, and a total of 103 differentially expressed genes were found. Fifty-two differentially expressed genes related to immunity and ferropotosis were identified using univariate Cox analysis. Stepwise regression was used to establish a Lasso-Cox risk score prognostic model consisting of four immune ferropotosis genes, and overall survival (OS) was significantly better in low-risk patients than in high-risk patients (training set: P < 0.001).In multivariate Cox regression analysis, the risk score was an independent predictor of OS (HR > 1, P < 0.001). Time-dependent ROC curve analysis indicates that the model has good predictive ability. The prognostic model was also well validated in the validation set and the total TCGA cohort. Subcellular fluorescence localization of model genes showed that ACADSB, CHAC1, and PLA2G6 were distributed in the cytoplasm, while LURAP1L was distributed in the nucleus. The expression of mRNA and protein suggested that ACADSB and CHAC1 were lower in renal carcinoma than in normal renal tissue, LURAP1L and PLA2G6 were higher in renal carcinoma. RNA sequencing localization analysis of ACADSB single-cell indicated that ACADSB was enriched in the distal tubule cluster. After mutation correlation analysis of model genes, 1.56% (7/448) patients were found to have genetic changes, ACADSB was significantly positively correlated with LURAP1L, and negatively correlated with CHAC1 and PLA2G6. CHAC1 was negatively correlated with LURAP1L. We found that CD8+T cells, regulatory T cells (Tregs), macrophage M0, and macrophage M1 levels were significantly higher in high-risk than low-risk patients. Among immune-related functions, we also found that the high-risk group had higher immune function in terms of immune checkpoint, proinflammatory, T-cell co-inhibition, and type II interferon response. Compared with the low-risk group, the high-risk group had a higher immune score in the immune microenvironment, a stronger immune escape ability, and a higher abundance of immune checkpoints. A novel prognostic model of immune ferropotosis-related genes (ACADSB, CHAC1, LURAP1L, and PLA2G6) was constructed, which can effectively predict the survival of patients with KIRC and play an important role in immune infiltration, microenvironment, and immune escape.