Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, China,
Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, China.
Ophthalmic Res. 2022;65(5):516-528. doi: 10.1159/000524505. Epub 2022 Apr 7.
Uveal melanoma (UM) is the most common primary intraocular malignancy among adults. Altered metabolism has been shown to contribute to the development of cancer closely, but the prognostic role of metabolism in UM remains to be explored. This study aimed to construct a metabolic-related signature for UM.
We collected the mRNA sequencing data and corresponding clinical information from The Cancer Genome Atlas and Gene Expression Omnibus databases. A univariate Cox regression analysis, the Lasso-penalized Cox regression analysis, and multivariate Cox regression analyses were used to construct a metabolic signature based on TCGA. The time-dependent ROC and Kaplan-Meier survival curves were calculated to validate the prognostic ability of the signature. The immune-related features and mutation profile were characterized by CIBERSORT and maftools between high- and low-risk groups.
A novel metabolic-related signature (risk score = -0.246SLC25A38 - 0.50186ABCA12 + 0.032CA12 + 0.086SYNJ2) was constructed to predict the prognosis of UM patients. In TCGA and GSE22138, the signature had high sensitivity and specificity in predicting the prognosis of UM patients (survival probability; p < 0.0001, p = 0.012) . Gene Ontology pathway enrichment analysis and GSEA were used to discriminate several significantly enriched metabolism-related pathways, including channel activity and passive transmembrane transporter activity, which may reveal the underlying mechanisms. The high-risk group had more immune cell infiltration and greater distribution of BAP1 mutations.
Our study developed a robust metabolic-gene signature based on TCGA to predict the prognosis of UM patients. The signature indicates a dysregulated metabolic microenvironment and provides new metabolic biomarkers and therapeutic targets for UM patients.
葡萄膜黑色素瘤（UM）是成年人中最常见的原发性眼内恶性肿瘤。已显示代谢改变与癌症的发展密切相关，但代谢在 UM 中的预后作用仍有待探索。本研究旨在构建 UM 的代谢相关特征。
我们从癌症基因组图谱和基因表达综合数据库中收集了 mRNA 测序数据和相应的临床信息。使用单变量 Cox 回归分析、Lasso 惩罚 Cox 回归分析和多变量 Cox 回归分析基于 TCGA 构建代谢特征。计算时间依赖性 ROC 和 Kaplan-Meier 生存曲线以验证特征的预后能力。通过 CIBERSORT 和 maftools 在高风险组和低风险组之间对免疫相关特征和突变谱进行了表征。
构建了一种新的代谢相关特征（风险评分=-0.246SLC25A38-0.50186ABCA12+0.032CA12+0.086SYNJ2），用于预测 UM 患者的预后。在 TCGA 和 GSE22138 中，该特征在预测 UM 患者的预后方面具有高灵敏度和特异性（生存概率;p<0.0001，p=0.012）。GO 通路富集分析和 GSEA 用于区分几个明显富集的代谢相关通路，包括通道活性和被动跨膜转运体活性，这可能揭示了潜在的机制。高风险组具有更多的免疫细胞浸润和更大的 BAP1 突变分布。
我们的研究基于 TCGA 开发了一种稳健的代谢基因特征，用于预测 UM 患者的预后。该特征表明代谢微环境失调，并为 UM 患者提供了新的代谢生物标志物和治疗靶点。
