本文由小咖机器人翻译整理

期刊来源：Nat Med

原文链接：https://doi.org/10.1038/s41591-024-02969-w

摘要内容如下：

神经-肿瘤相互作用驱动胶质瘤生长，这在临床前模型中得到证实，但临床验证有限。我们提出了胶质母细胞瘤的表观遗传学定义的神经信号，该信号可独立预测患者的生存率。我们使用神经细胞的参考信号对肿瘤DNA进行去卷积，并将样本分类为低度或高度神经肿瘤。高神经胶质母细胞瘤表现出低甲基化的CpG位点和与突触整合相关的基因上调。单细胞转录组分析显示，高神经胶质母细胞瘤中存在大量恶性干细胞样细胞，主要是神经谱系。这些细胞进一步分为神经祖细胞样、星形胶质细胞样和少突胶质细胞祖细胞样，以及少突胶质细胞和兴奋性神经元。与这些发现一致的是，高神经胶质母细胞瘤细胞在体外和体内产生神经元-神经胶质瘤突触形成，并且在异种移植后表现出不利的存活率。在患者中，高神经信号与总体生存率和无进展生存率下降相关。高神经肿瘤在脑磁图和静息态磁共振成像中也表现出功能连接增加，并且可以通过患者血浆中的DNA分析物和脑源性神经营养因子来检测。神经信号的预后重要性在诊断为弥漫性中线胶质瘤的患者中得到了进一步验证。我们的研究在高级别胶质瘤中提出了一种表观遗传学定义的恶性神经信号，该信号与预后相关。高神经胶质瘤可能需要最大限度的手术切除方法来改善预后。

英文原文如下：

Abstracts

Neural-tumor interactions drive glioma growth as evidenced in preclinical models, but clinical validation is limited. We present an epigenetically defined neural signature of glioblastoma that independently predicts patients' survival. We use reference signatures of neural cells to deconvolve tumor DNA and classify samples into low- or high-neural tumors. High-neural glioblastomas exhibit hypomethylated CpG sites and upregulation of genes associated with synaptic integration. Single-cell transcriptomic analysis reveals a high abundance of malignant stemcell-like cells in high-neural glioblastoma, primarily of the neural lineage. These cells are further classified as neural-progenitor-cell-like, astrocyte-like and oligodendrocyte-progenitor-like, alongside oligodendrocytes and excitatory neurons. In line with these findings, high-neural glioblastoma cells engender neuron-to-glioma synapse formation in vitro and in vivo and show an unfavorable survival after xenografting. In patients, a high-neural signature is associated with decreased overall and progression-free survival. High-neural tumors also exhibit increased functional connectivity in magnetencephalography and resting-state magnet resonance imaging and can be detected via DNA analytes and brain-derived neurotrophic factor in patients' plasma. The prognostic importance of the neural signature was further validated in patients diagnosed with diffuse midline glioma. Our study presents an epigenetically defined malignant neural signature in high-grade gliomas that is prognostically relevant. High-neural gliomas likely require a maximized surgical resection approach for improved outcomes.

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