Development and Validation of a Novel Metabolic Signature-Based Prognostic Model for Uveal Melanoma

PURPOSE: Uveal melanoma (UM) is the most common primary malignant tumor with poor prognosis. The role of metabolism-related genes in the prognosis of UM remains unrevealed. This study aimed to establish and validate a prognostic prediction model for UM based on metabolism-related genes. METHODS: Gene expression profiles and clinicopathological information were downloaded from The Cancer Genome Atlas, and the Gene Expression Omnibus database. Univariable Cox regression, least absolute shrinkage and selection operator Cox regression, and stepwise regression were performed to establish the model. Kaplan-Meier survival analysis, receiver operating characteristic (ROC) curve analysis, and calibration and discrimination analyses were used to evaluate the prognostic model. RESULTS: Three metabolism-related genes, carbonic anhydrase 12, acyl-CoA synthetase long-chain family member 3, and synaptojanin 2, and three clinicopathological parameters (i.e., age, gender, and metastasis staging) were identified to establish the model. The risk score was found to be an independent prognostic factor for UM survival. High-risk patients demonstrated significantly poorer prognosis than low-risk patients. ROC analysis suggested the promising prognostic efficiency of the model. The calibration curve manifested satisfactory agreement between the predicted and observed risk. A nomogram and online survival calculator were developed to predict the survival probability. CONCLUSIONS: The novel metabolism-based prognostic model could accurately predict the prognosis of UM patients, which facilitates the prediction of the survival probability by both ophthalmologists and patients with the online dynamic nomogram. TRANSLATIONAL RELEVANCE: The dynamic nomogram links gene expression profiles to clinical prognosis of UM and is useful to evaluate the survival probability.