Hypoxia-related lncRNA correlates with prognosis and immune microenvironment in uveal melanoma.

IF 5.3 2区 医学 Q1 ONCOLOGY
Yu Chen, Shen Chen, Zhenkai Wu, Quan Cheng, Dan Ji
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Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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lncRNA与葡萄膜黑色素瘤的预后和免疫微环境有关
背景:缺氧相关基因与各种实体恶性肿瘤的预后有关。然而,缺氧相关长非编码 RNA(HRLs)在葡萄膜黑色素瘤(UVM)中的作用仍不清楚。本研究旨在鉴定与葡萄膜黑色素瘤预后相关的HRLs,并开发一种新的风险特征来预测患者的预后:方法:从癌症基因组图谱(The Cancer Genome Atlas)中获得了80个UVM样本的数据。利用Cox单变量分析和Pearson相关分析筛选出预后相关的HRL。利用Lasso分析构建了HRL特征,并进行了基因富集分析,以探索HRL与免疫特征之间的关联。细胞计数试剂盒-8测定了人葡萄膜黑色素瘤(MuM2B)细胞的繁殖,Transwell和伤口愈合实验评估了肿瘤的侵袭和迁移。利用定量 PCR 评估了炎症因子和巨噬细胞极化:结果:共筛选出621个预后HRL,并在12个HRL中构建了预后HRL。风险评分与 UVM 患者的生存时间有明显相关性。此外,HRL与多种关键免疫检查点相关,揭示了免疫疗法的可能靶点。免疫相关通路在高风险组中高度富集。LINC02367是一种保护性HRL,它与UVM患者的肿瘤微环境和生存时间有关。在体外,LINC02367能显著影响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的极化,从而影响免疫微环境:我们发现了一种新的HRL特征,可用于预测紫癜患者的预后。HRL是治疗紫癜的潜在生物标志物和治疗靶点。
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来源期刊
CiteScore
10.90
自引率
1.70%
发文量
360
审稿时长
1 months
期刊介绍: Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.
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