Abstract
BackgroundUveal melanoma(UVM) is the most common intraocular malignancy and has a poor prognosis. The clinical significance of necroptosis(NCPS) in UVM is unclear.MethodsWe first identified necroptosis genes in UVM by single-cell analysis of the GSE139829 dataset from the GEO database and weighted co-expression network analysis of TCGA data. COX regression and Lasso regression were used to construct the prognostic model. Then survival analysis, immune microenvironment analysis, and mutation analysis were carried out. Finally, cell experiments were performed to verify the role of ITPA in UVM.ResultBy necroptosis-related prognostic model, UVM patients in both TCGA and GEO cohorts could be classified as high-NCPS and low-NCPS groups, with significant differences in survival time between the two groups (P<0.001). Besides, the high-NCPS group had higher levels of immune checkpoint-related gene expression, suggesting that they might be more likely to benefit from immunotherapy. The cell experiments confirmed the role of ITPA, the most significant gene in the model, in UVM. After ITPA was knocked down, the activity, proliferation, and invasion ability of the MuM-2B cell line were significantly reduced.ConclusionOur study can provide a reference for the diagnosis and treatment of patients with UVM.
Highlights
Uveal melanoma (UVM) is a rare tumor type, it is the most common intraocular malignancy [1]
Our study can provide a reference for the diagnosis and treatment of patients with uveal melanoma (UVM)
68 genes related to necroptosis were input using the “PercentageFeatureSet” function, and the percentage of necroptosis genes in each cell was obtained
Summary
Uveal melanoma (UVM) is a rare tumor type, it is the most common intraocular malignancy [1]. It is worth mentioning that UVM and cutaneous malignant melanoma (the most common type of melanoma) have significant differences in risk factors, pathological features, and treatment outcomes [3, 4]. Immune checkpoint inhibitor therapies, such as PD-1/PDL-1 or CTLA-4 inhibitors, that have made breakthroughs in the treatment of other solid tumors with a high mutation load, are being investigated for their utility in UVM [9]. At present, a large number of UVM patients do not respond well to immune checkpoint inhibitors, which may be related to low mutation load, new immune checkpoint acquisition, and the production of immunosuppressive factors [10]. Uveal melanoma(UVM) is the most common intraocular malignancy and has a poor prognosis. The clinical significance of necroptosis(NCPS) in UVM is unclear
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