TF和DNA甲基化协同驱动lncRNAs调控转移性皮肤黑色素瘤
Role of lncRNAs driven by TFs and DNA methylation in prognosis and immune microenvironment of metastatic cutaneous melanoma
摘要
皮肤黑色素瘤（CM）是一种恶性肿瘤，转移是导致患者死亡的主要原因。差异表达的lncRNAs在肿瘤预后模型中发挥着重要作用，但表观遗传学修饰的lncRNA在转移性CM（MCM）中的预后影响仍有待阐明。本研究旨在分析转录因子（TFs）和DNA甲基化（DNAm）探针驱动的lncRNA对MCM预后和免疫微环境的影响。检测到差异表达lncRNAs启动子区域内的探针。Searman相关性分析显示，该探针对lncRNAs大多具有负调控作用。由于转录因子识别特定的基序并与探针周围的DNA序列结合，我们系统地鉴定了候选转录因子。通过整合转录组/甲基组数据和相关性分析，获得了TF-Probe-lncRNA三元组关系。进而构建了MCM患者的风险评分模型，发现HEY2-cg14245202-RP11-219G17.4三元组可以有效地将MCM患者分为高风险组和低风险组。与低风险患者相比，高风险患者的存活率明显较低。富集分析表明，与TFs和探针相互作用的lncRNAs与免疫调节和肿瘤转移密切相关。免疫微环境分析表明，MCM的免疫逃逸现象可能与间充质干细胞的数量有关，肥大细胞的浸润和内皮屏障的功能损失可能介导黑色素瘤细胞的转移进展。此外，高危MCM患者的免疫治疗效果有限。
Abstract
Cutaneous melanoma (CM) is a malignant tumor, and metastasis represents the leading cause of death in patients. Differentially expressed lncRNAs exert significant functions within tumor prognostic models, yet the prognostic impact of epigenetically modified lncRNAs in metastatic CM (MCM) remains to be elucidated. This study aimed to analyze the impact of lncRNAs driven by transcription factors (TFs) and DNA methylation (DNAm) probes on the MCM prognosis and the immune microenvironment. Probes within the promoter regions of differentially expressed lncRNAs were detected. Spearman correlation analysis revealed that the probe had mostly negative regulation on lncRNAs. Since TFs recognize specific motifs and bind to the DNA sequences around probes, we systematically identified candidate TFs. Through integrating transcriptome/methylome data and the correlation analysis, TF-Probe-lncRNA relationships were obtained. We constructed a risk score model for MCM patients, and found that the HEY2-cg14245202-RP11-219G17.4 triplet could effectively stratify MCM patients into high- and low-risk groups. High-risk patients exhibited significantly lower survival rates compared to the low-risk patients. Enrichment analysis suggested that the lncRNAs interacted with both TFs and probes were closely related to immune regulation, and metastasis of tumors. The immune microenvironment analysis revealed thatt the immune escape phenomenon of MCM may be related to the number of mesenchymal stem cells, and the infiltration of mast cells and endothelial barrier loss may mediate the metastatic progression of melanoma cells. In addition, high-risk MCM patients have limited efficacy in immunotherapy.关键词
生物数学/转移性皮肤黑色素瘤/TF和DNAm驱动的lncRNAs/免疫微环境/预后模型。Key words
Biomathematics/ Metastatic cutaneous melanoma/ LncRNAs driven by TFs and DNAm/ Immune microenvironment/ Prognostic model.引用本文复制引用
徐星悦,张旭.TF和DNA甲基化协同驱动lncRNAs调控转移性皮肤黑色素瘤[EB/OL].(2026-04-07)[2026-04-08].http://www.paper.edu.cn/releasepaper/content/202604-59.学科分类
遗传学/分子生物学/生物化学
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