Abstract
Uveal melanoma (UVM) is the most common primary ocular malignancy in adults and involves several types of regulated cell death. Cuproptosis is a novel method of regulating cell death by binding lipoylated TCA cycle proteins. There is still no research on the relationship between cuproptosis-related genes (CRGs) and UVM. Here, we aimed to develop a prognostic CRG signature for UVM. After a prognostic CRG signature was constructed, we determined the relationship between the signature and immune infiltration, bioinformatics analysis and experimental validation. Finally, a prognostic cuproptosis-related three-gene (CRTG) signature was constructed, which comprised ORAI2, ACADSB and SLC47A1. The risk score of the CRTG signature was negatively correlated with the overall survival (OS) and progression-free survival (PFS) of patients, which revealed strong predictive ability and its independent prognostic value. In addition, we found that the risk score was negative for chromosomes 3 and 6p, and positive for 8q, and high-risk UVM patients showed an increase in protumor immune infiltrates and a high expression of immune checkpoints. Finally, experimental validation verified that the migratory ability of MUM-2B cells was suppressed by the knockdown of the identified genes in vitro. We constructed a CRTG signature that is helpful in predicting prognosis and guiding treatment for patients with UVM.