Chen Yu, Chen Shen, Wu Zhenkai, Cheng Quan, Ji Dan
Department of Ophthalmology, Hunan Key Laboratory of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
Cancer Cell Int. 2024 Oct 9;24(1):336. doi: 10.1186/s12935-024-03509-9.
Hypoxia-related genes are linked to the prognosis of various solid malignant tumors. However, the role of hypoxia-related long non-coding RNAs (HRLs) in uveal melanoma (UVM) remains unclear. This study aimed to identify HRLs associated with UVM prognosis and develop a novel risk signature to predict patient outcomes.
Data from 80 UVM samples were obtained from The Cancer Genome Atlas. Prognostic HRLs were screened using Cox univariate and Pearson correlation analyses. HRL signature were constructed using Lasso analysis, and gene enrichment analysis was performed to explore the association between HRLs and immune features. Cell Counting Kit-8 assay was used to measure the propagation of human uveal melanoma (MuM2B) cells, while tumor invasion and migration were evaluated using Transwell and wound-healing experiments. Inflammatory factors and macrophage polarization were evaluated using quantitative PCR.
In total, 621 prognostic HRLs were screened and constructed in 12 HRLs. The risk score showed a significant correlation with the survival time of patients with UVM. Additionally, HRL correlated with diverse key immune checkpoints, revealing possible targets for immunotherapy. Immune-related pathways were highly enriched in the high-risk group. LINC02367, a protective HRL, was associated with the tumor microenvironment and survival time of patients with UVM. In vitro, LINC02367 significantly influenced MuM2B proliferation and migration. It also modulated macrophage polarization by regulating inflammatory factor levels, thereby affecting the immune microenvironment.
We developed a novel HRL signature to predict prognosis in patients with UVM. HRLs are potential biomarkers and therapeutic targets for the treatment of UVM.
缺氧相关基因与多种实体恶性肿瘤的预后相关。然而，缺氧相关长链非编码RNA（HRLs）在葡萄膜黑色素瘤（UVM）中的作用仍不清楚。本研究旨在鉴定与UVM预后相关的HRLs，并开发一种新的风险特征来预测患者预后。
从癌症基因组图谱获取80例UVM样本的数据。使用Cox单因素分析和Pearson相关分析筛选预后HRLs。使用Lasso分析构建HRL特征，并进行基因富集分析以探索HRLs与免疫特征之间的关联。使用细胞计数试剂盒-8法检测人葡萄膜黑色素瘤（MuM2B）细胞的增殖，同时使用Transwell和伤口愈合实验评估肿瘤侵袭和迁移。使用定量PCR评估炎症因子和巨噬细胞极化。
共筛选出621个预后HRLs，并构建了包含12个HRLs的特征。风险评分与UVM患者的生存时间显著相关。此外，HRLs与多种关键免疫检查点相关，揭示了免疫治疗的潜在靶点。免疫相关通路在高危组中高度富集。保护性HRL LINC02367与UVM患者的肿瘤微环境和生存时间相关。在体外，LINC02367显著影响MuM2B的增殖和迁移。它还通过调节炎症因子水平来调节巨噬细胞极化，从而影响免疫微环境。
我们开发了一种新的HRL特征来预测UVM患者的预后。HRLs是UVM治疗的潜在生物标志物和治疗靶点。
