Department of Ophthalmology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
Int J Mol Sci. 2023 Jul 12;24(14):11358. doi: 10.3390/ijms241411358.
Uveal melanoma (UVM) is the most common primary ocular malignancy in adults and involves several types of regulated cell death. Cuproptosis is a novel method of regulating cell death by binding lipoylated TCA cycle proteins. There is still no research on the relationship between cuproptosis-related genes (CRGs) and UVM. Here, we aimed to develop a prognostic CRG signature for UVM. After a prognostic CRG signature was constructed, we determined the relationship between the signature and immune infiltration, bioinformatics analysis and experimental validation. Finally, a prognostic cuproptosis-related three-gene (CRTG) signature was constructed, which comprised ORAI2, ACADSB and SLC47A1. The risk score of the CRTG signature was negatively correlated with the overall survival (OS) and progression-free survival (PFS) of patients, which revealed strong predictive ability and its independent prognostic value. In addition, we found that the risk score was negative for chromosomes 3 and 6p, and positive for 8q, and high-risk UVM patients showed an increase in protumor immune infiltrates and a high expression of immune checkpoints. Finally, experimental validation verified that the migratory ability of MUM-2B cells was suppressed by the knockdown of the identified genes in vitro. We constructed a CRTG signature that is helpful in predicting prognosis and guiding treatment for patients with UVM.
葡萄膜黑色素瘤(UVM)是成年人中最常见的原发性眼内恶性肿瘤,涉及几种类型的受调控的细胞死亡。铜死亡是一种通过结合脂酰化 TCA 循环蛋白来调节细胞死亡的新方法。目前还没有关于铜死亡相关基因(CRGs)与 UVM 之间关系的研究。在这里,我们旨在为 UVM 开发一个预后的 CRG 特征。在构建预后的 CRG 特征后,我们确定了特征与免疫浸润、生物信息学分析和实验验证之间的关系。最后,构建了一个预后的铜死亡相关的三个基因(CRTG)特征,该特征包括 ORAI2、ACADSB 和 SLC47A1。CRTG 特征的风险评分与患者的总生存(OS)和无进展生存(PFS)呈负相关,这揭示了其强大的预测能力及其独立的预后价值。此外,我们发现风险评分对染色体 3 和 6p 为阴性,对 8q 为阳性,高危 UVM 患者的促肿瘤免疫浸润增加,免疫检查点表达升高。最后,实验验证证实,体外敲低鉴定基因可抑制 MUM-2B 细胞的迁移能力。我们构建了一个 CRTG 特征,有助于预测 UVM 患者的预后和指导治疗。