The potential prognostic and immunological roles of N7-methylguanosine (m7G) in uveal melanoma

Abstract

Objective Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Recently, RNA modifications have received increasing attention and have been shown to regulate tumorigenesis and immune response. However, the specific roles of N7-methylguanosine (m7G) on the prognosis, tumour immune microenvironment and immunotherapy in UM remain poorly understood. Methods Gene expression data and clinical data of 80 and 28 UM cases were obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases, respectively. Of the 26 m7G regulators, eight prognosis-related m7G regulators were identified and analyzed for their correlations with survival outcomes, immune cell infiltration and immunotherapy sensitivity. Single-cell data were downloaded and used to validate the changes in the immune microenvironment. Results A total of eight prognostic m7G regulators––EIF3D, EIF4E2, EIF4E3, EIF4G3, NUDT16, NUDT16L1, SNUPN and WDR4––were identified to construct a m7G-related risk model. Patients were divided into high- and low-risk groups based on this model. The high-risk group was characterized by a poorer prognosis and higher infiltration abundance of immunosuppressed CD8 T cells. Immune cell depletion markers were significantly overexpressed in high-risk patients and predicted better response to immunotherapy. Additionally, we found that m7G regulators were most closely related to the function of the monocyte/macrophage. Conclusions We constructed a risk model comprising eight m7G regulators with good predictive power for prognosis and immunotherapy sensitivity. We also found that m7G regulators are associated with monocyte/macrophage immunity in UM. These novel findings may provide new insights into m7G regulators as prognostic and immunotherapeutic biomarkers for UM and therapies targeting m7G regulators.