Comprehensive analysis of Cuproptosis regulators in ccRCC and prospects for immunotherapy

Abstract

Based on data from the Cancer Genome Atlas (TCGA) on renal clear cell carcinoma(ccRCC), we noted different expression profiles of Cuproptosis regulators in ccRCC and normal tissues, and we also found that Cuproptosis regulators were associated with PD-L1 expression.Based on the expression levels of Cuproptosis regulators in ccRCC, two independent isoforms were identified by consensus clustering analysis. Cluster 1 showed lower histological tumor stage and grade, more favorable prognosis, and higher PD-L1 expression compared to cluster 2.CIBERSORT analysis revealed that cluster 2 contained higher levels of T cell CD8+,T cell regulatory (Tregs), NK cell activated and T cell follicular helper, whereas cluster 1 was more relevant to Monocytes, Macrophage M1, Macrophage M2, T cell and Mast cell activated.After analysis, we identified DLAT as a potential key regulator of Cuproptosis associated with immune infiltration, and its low expression showed a poor prognosis and positively correlated with PD-L1 expression in ccRCC.In addition, we performed a pan-cancer analysis of this gene, and DLAT expression was strongly correlated with the expression of immune checkpoint-related genes, particularly PD-L1, with unfavorable prognosis in multiple cancer types.In conclusion, this study reveals the potential role of Cuproptosis regulators in ccRCC and identifies biomarkers associated with Cuproptosis for prognosis and immunotherapy prediction.