Role of a cuproptosis-related prognostic signature in uveal melanoma tumor microenvironment and immune responses

Abstract

Abstract Background The most common intraocular cancer is uveal melanoma (UVM). A unique mechanism of cell death, known as cuproptosis, is linked to the development, prognosis, and immunity of tumors. Cuproptosis-related genes (CRGs) may play a role in UVM prognosis; however, this remains unclear. Methods We performed single-cell analysis and unsupervised cluster analysis from the Gene Expression Omnibus and The Cancer Genome Atlas (TCGA)-UVM databases. Weighted gene co-expression network analysis (WGCNA) was used to identify genes associated with molecular subtypes and cuproptosis scores. The least absolute shrinkage and selection operator, and multivariate Cox analysis were then used to build a prognostic risk model. Using Cox analysis, independent prognostic indicators were confirmed. Results We identified two prognostic genes (DLD and PDHB) to construct the CRGs signature. Using Cox regression analysis, the risk score was found to be an independent prognostic predictor. Significantly more patients in the low-risk group survived than those in the high-risk group. Meanwhile, nine immune cells (Monocytes, M1 macrophages, T cells CD8), immune score, stromal score, two immune cells and related functions (aDCs and Th2 cells), and immune checkpoint expression (ICOS, CD48, and CD70) were all related to the risk score. The correlation of DLD and Wnt.C59, Sinularin were investigated. And meanwhile, it was confirmed that PDHB was significantly relevant to fibroblasts and NK cells. Finally, the expressions of DLD and PDHB might be affected by the KEGG pathway of cell cycle and Ubiquitin mediated proteolysis. Conclusion This study identified cuproptosis-associated prognostic genes for UVM and provided new insights into its treatment.