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一种新型糖酵解相关特征可预测葡萄膜黑色素瘤的预后和免疫浸润。

A Novel Glycolysis-Related Signature for Predicting the Prognosis and Immune Infiltration of Uveal Melanoma.

机构信息

Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, China,

Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, China.

出版信息

Ophthalmic Res. 2023;66(1):692-705. doi: 10.1159/000529818. Epub 2023 Mar 1.

DOI:10.1159/000529818
PMID:36858025
Abstract

INTRODUCTION

As the most common aggressive intraocular cancer in adults, uveal melanoma (UVM) threatens the survival and vision of many people. Glycolysis is a novel hallmark of cancer, but the role of glycolysis-related genes in UVM prognosis remains unknown. The purpose of the study was to establish a glycolysis-related gene signature (GRGS) to predict UVM prognosis.

METHODS

Raw data were obtained from TCGA-UVM and GSE22138 datasets. The GRGS was established by univariate, LASSO, and multivariate Cox regression analyses. Kaplan-Meier survival and time-dependent receiver operating characteristic curves were used to evaluate the predictive ability of the GRGS. The relationships of the GRGS with infiltrating immune cell levels and mutations were analyzed with CIBERSORT and maftools.

RESULTS

A novel GRGS (risk score = 0.690861ISG20 + 0.070991MET - 0.227520SDC2 + 0.690223FBP1 + 0.048008CLN6 - 0.128520SDC3) was developed for predicting UVM prognosis. The GRGS had robust predictive stability in UVM. Enrichment annotation suggested that the high-risk group had stronger adaptive immune responses and that the low-risk group had more innate immune cell infiltration. Moreover, BAP1 mutation was related to high risk, and SF3B1 mutation was related to low risk.

CONCLUSIONS

This study developed and validated a novel GRGS to predict UVM prognosis and immune infiltration. The signature revealed an association between glycolysis-related genes and the tumor microenvironment, providing new insights into the role of glycolysis in UVM.

摘要

简介

葡萄膜黑色素瘤(uveal melanoma,UVM)作为成年人中最常见的侵袭性眼内癌,威胁着许多人的生存和视力。糖酵解是癌症的一个新标志,但糖酵解相关基因在 UVM 预后中的作用尚不清楚。本研究旨在建立一个糖酵解相关基因特征(glycolysis-related gene signature,GRGS)来预测 UVM 预后。

方法

从 TCGA-UVM 和 GSE22138 数据集获取原始数据。通过单变量、LASSO 和多变量 Cox 回归分析建立 GRGS。使用 Kaplan-Meier 生存和时间依赖性接受者操作特征曲线评估 GRGS 的预测能力。通过 CIBERSORT 和 maftools 分析 GRGS 与浸润免疫细胞水平和突变的关系。

结果

建立了一个新的 GRGS(风险评分=0.690861ISG20+0.070991MET-0.227520SDC2+0.690223FBP1+0.048008CLN6-0.128520SDC3)用于预测 UVM 预后。GRGS 在 UVM 中具有稳健的预测稳定性。富集注释表明,高风险组具有更强的适应性免疫反应,而低风险组具有更多的固有免疫细胞浸润。此外,BAP1 突变与高风险相关,SF3B1 突变与低风险相关。

结论

本研究开发并验证了一个新的 GRGS 来预测 UVM 预后和免疫浸润。该特征揭示了糖酵解相关基因与肿瘤微环境之间的关联,为糖酵解在 UVM 中的作用提供了新的见解。

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