Abstract
BACKGROUND: Cuproptosis is a recently discovered form of nonapoptotic programmed cell death. However, no research on cuproptosis in the context of adrenocortical carcinoma has been conducted, and the prognostic value of assessing cuproptosis remains unclear. METHODS: In this study, we established comprehensive models to assess gene expression changes, mutation status, and prognosis prediction and developed a prognostic nomogram for cuproptosis-related genes. Using data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Genotype-Tissue Expression (GTEx) databases, an analysis of 11 cuproptosis-related genes was performed. Additionally, a risk scoring method and nomogram were used to assess the relationships among cuproptosis-associated genes, transcript expression, clinical characteristics, and prognosis. The connections among tumors, immune checkpoints, and immune infiltration were also analyzed. RESULTS: The patterns observed in patients with adrenocortical carcinoma who were assessed using cuproptosis-associated risk scores provide useful information for understanding gene mutations, clinical outcomes, immune cell infiltration, and immune checkpoint analysis results. FDX1, LIPT1, MTF1, COX11, CYP2D6, DLAT, ATP7Band CDKN2A were differentially expressed in patients with adrenocortical carcinoma and normal controls. In addition, higher risk scores were significantly associated with poor overall survival and progression-free interval. The nomogram model subsequently developed to facilitate the clinical application of the analysis showed good predictive and calibration capabilities. GSE10927 and GSE33371 were used for independent cohort validation. Moreover, CDKN2A, FDX1, and other cuproptosis-related genes were significantly associated with immune infiltration and checkpoints. CONCLUSION: We confirmed that our model had excellent predictive ability in patients with adrenocortical carcinoma. Therefore, an in-depth evaluation of patients using cuproptosis-related risk scores is clinically essential and can assist in therapy in the future.