The Prognostic Potential of Cuproptosis and Cuproptosis-Related Alteration of Clear Cell Renal Cell Carcinoma

Abstract

Aim To study whether the novel copper ionophores induced cell death would impact the prognosis of clear cell renal cell carcinoma (ccRCC) and subsequently influence the tumor microenvironment (TME). Methods The differential expression of 10 cuproptosis and 40 TME-pathway-related genes were measured between 531 tumor samples and 71 adjacent kidney samples in The Cancer Genome Atlas (TCGA) database. The risk score model was constructed with LASSO-cox to predict the prognosis of ccRCC patients in the training cohort (331 patients). Afterward, the risk model was reinforced in the validation cohort and the entire cohort. To study the biological function of the hub genes in-depth, nomogram and function enrichment were employed. Subsequently, the ESTIMATE analysis, TMEscore analysis and CIBERSORT algorithm were employed to To further observe the impact of these hub-genes on the TME. Results Differentially expressed genes (DEGs) were identified between tumor and normal samples. Twenty-one DEGs were used for the construction of LASSO-cox regression and a risk model with 10 hub genes were screened out to predict the prognosis of ccRCC patients. Patients from the High-Score group had a worse overall survival (OS). Besides, though many immunosuppressive cytokines encoding genes contributed to the High-Score group, this group showed a better immune response when compared to the Low-Score group. In addition, the High-Score group exhibited a significantly higher proportion of several anti-tumor lymphocytes and a lower proportion of immunosuppressive M2-like macrophages. However, the T follicular helper cells and regulatory T cells also showed higher proportion in the High-Score group. Conclusion The risk score model showed promising and predictive accuracy for the prognosis of ccRCC patients. Besides that, the cuproptosis based therapy is worth further studying regarding the ccRCC tumor and TME.