Identification of a prognostic model using cuproptosis-related genes in uveal melanoma

Abstract

The most common intraocular malignancy in adults remains uveal melanoma (UVM), and those with metastatic disease have a poor outlook. Proliferation, angiogenesis, and metastasis of tumor cells can be triggered by cuproptosis, affecting the survival of cancer patients. Nonetheless, cuproptosis-related genes (CRGs) have not been identified in UVM. In this study, we analyzed 10 CRGs in 80 patients with UVM in the Cancer Genome Atlas (TCGA) database regarding the alterations of the genes including copy number variation and methylation. We further constructed a prognostic gene model using these CRGs and built the risk score formula. Univariate and multivariate Cox regression was applied to validate the risk score as an independent prognostic factor. The prognostic model was validated using 63 UVM samples from the GSE22138 cohort, an independent validation data set. Based on the risk scores for 80 patients with UVM from TCGA, we categorized the patients into high- and low-risk groups. Differentially expressed genes (DEGs) between groups were enriched in allograft rejection, hypoxia, glycolysis, TNFα signaling via NF-κB, and interferon-γ responses via Gene set enrichment analysis (GSEA). CD8 T cells and exhausted T cells were notably enriched in the high-risk group. In conclusion, the alteration of CRGs is related to patients with UVM, and the constructed CRG-related model may be helpful to predict the prognosis of such patients.