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A five‐CpG signature of microRNA methylation in non‐G‐CIMP glioblastoma

机译：非G-CIMP胶质母细胞瘤中microRNA甲基化的5-CpG标记

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Aims DNA methylation has been found to regulate microRNAs (miRNAs) expression, but the prognostic value of miRNA‐related DNA methylation aberration remained largely elusive in cancers including glioblastomas (GBMs). This study aimed to investigate the clinical and biological feature of miRNA methylation in GBMs of non‐glioma‐CpG island methylator phenotype (non‐G‐CIMP). Methods Prognostic miRNA methylation loci were analyzed, with TCGA and Rennes cohort as training sets, and independent datasets of GBMs and low‐grade gliomas (LGGs) were obtained as validation sets. Different statistical and bioinformatic analysis and experimental validations were performed to clinically and biologically characterize the signature. Results We identified and validated a risk score based on methylation status of five miRNA‐associated CpGs which could predict survival of GBM patients in a series of training and validation sets. This signature was independent of age and O‐6‐methylguanine‐DNA methyltransferase ( MGMT ) promoter methylation status. The risk subgroup was associated with angiogenesis and accordingly differential responses to bevacizumab‐contained therapy. MiRNA target analysis and in vitro experiments further confirmed the accuracy of this signature. Conclusion The five‐CpG signature of miRNA methylation was biologically relevant and was of potential prognostic and predictive value for GBMs. It might be of help for improving individualized treatment.

机译：目的是发现DNA甲基化可调控microRNA（miRNA）的表达，但与miRNA相关的DNA甲基化畸变的预后价值在包括胶质母细胞瘤（GBM）在内的癌症中仍然遥遥无期。本研究旨在调查非神经胶质瘤CpG岛甲基化者表型（non-G-CIMP）GBM中miRNA甲基化的临床和生物学特征。方法以TCGA和雷恩队列为训练集，分析预后的miRNA甲基化位点，并获得独立的GBM和低级神经胶质瘤（LGG）数据集作为验证集。进行了不同的统计和生物信息学分析以及实验验证，以对签名进行临床和生物学表征。结果我们基于五种与miRNA相关的CpG的甲基化状态，确定并验证了风险评分，这些风险评分可以通过一系列培训和验证集来预测GBM患者的生存。此签名与年龄和O-6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）启动子的甲基化状态无关。危险亚组与血管生成有关，因此对贝伐单抗治疗的反应不同。 MiRNA靶标分析和体外实验进一步证实了该签名的准确性。结论miRNA甲基化的5 CpG标记具有生物学相关性，对GBM具有潜在的预后和预测价值。这可能有助于改善个体化治疗。

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《CNS neuroscience & therapeutics.》 |2019年第9期|共14页
作者
En‐Ming Kang; An‐An Yin; Ya‐Long He; Wei‐Jun Chen; Amandine Etcheverry; Marc Aubry; Jill Barnholtz‐Sloan; Jean Mosser; Wei Zhang; Xiang Zhang;
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中图分类神经病学与精神病学;
关键词
angiogenesisDNA methylation signatureglioblastomamiRNAprognostication;

机译：血管生成DNA甲基化签名胶质母细胞瘤RNA预后;

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1. Erratum: MGMT methylation analysis of glioblastoma on the Infinium methylation BeadChip identifies two distinct CpG regions associated with gene silencing and outcome, yielding a prediction model for comparisons across datasets, tumor grades, and CIMP-status (Acta Neuropathol (2012) 124 (547-560) DOI:10.1007/s00401-012-1016-2) [J] . BadyP., SciuscioD., DiserensA.-C., Acta Neuropathologica . 2013,第1期

机译：勘误表：在Infinium甲基化BeadChip上对胶质母细胞瘤进行MGMT甲基化分析，鉴定出两个与基因沉默和结果相关的截然不同的CpG区域，从而为在数据集，肿瘤等级和CIMP状态之间进行比较提供了一个预测模型（Acta Neuropathol（2012）124（547- 560）DOI：10.1007 / s00401-012-1016-2）
2. MGMT methylation analysis of glioblastoma on the Infinium methylation BeadChip identifies two distinct CpG regions associated with gene silencing and outcome, yielding a prediction model for comparisons across datasets, tumor grades, and CIMP-status [J] . BadyP., SciuscioD., DiserensA.-C., Acta Neuropathologica . 2012,第4期

机译：在Infinium甲基化BeadChip上对胶质母细胞瘤进行MGMT甲基化分析，鉴定出两个与基因沉默和结果相关的不同CpG区域，从而提供了一个预测模型，可用于数据集，肿瘤等级和CIMP状态的比较
3. MGMT methylation analysis of glioblastoma on the Infinium methylation BeadChip identifies two distinct CpG regions associated with gene silencing and outcome, yielding a prediction model for comparisons across datasets, tumor grades, and CIMP-status [J] . Pierre Bady, Davide Sciuscio, Annie-Claire Diserens, Acta Neuropathologica . 2012,第4期

机译：在Infinium甲基化BeadChip上对胶质母细胞瘤进行MGMT甲基化分析，鉴定出两个与基因沉默和结果相关的不同CpG区域，从而提供了一个预测模型，用于在数据集，肿瘤等级和CIMP状态之间进行比较
4. MethylCRF, an Algorithm for Estimating Absolute Methylation Levels at Single CpG Resolution from Methylation Enrichment and Restriction Enzyme Sequencing Methods [C] . Michael Stevens, Jeffrey B. Cheng, Mingchao Xie, Annual international conference on research in computational molecular biology . 2013

机译：MethylCRF，一种从甲基化富集和限制酶测序方法估算单CpG分辨率下绝对甲基化水平的算法
5. A study of microRNAs associated with multiple myeloma pathogenesis and microRNAs/TP53 feedback circuit in human cancers, multiple myeloma and glioblastoma multiforme. [D] . Suh, Sung-Suk. 2012

机译：在人类癌症，多发性骨髓瘤和多形性胶质母细胞瘤中与多发性骨髓瘤发病机制相关的microRNA和microRNA / TP53反馈回路的研究。
6. MGMT methylation analysis of glioblastoma on the Infinium methylation BeadChip identifies two distinct CpG regions associated with gene silencing and outcome yielding a prediction model for comparisons across datasets tumor grades and CIMP-status [O] . Pierre Bady, Davide Sciuscio, Annie-Claire Diserens, -1

机译：在Infinium甲基化BeadChip上对胶质母细胞瘤进行MGMT甲基化分析确定了两个与基因沉默和结果相关的不同CpG区域从而提供了一个预测模型用于在数据集肿瘤等级和CIMP状态之间进行比较
7. Erratum to: MGMT methylation analysis of glioblastoma on the Infinium methylation BeadChip identifies two distinct CpG regions associated with gene silencing and outcome, yielding a prediction model for comparisons across datasets, tumor grades, and CIMP-status [O] . Bady, P, Sciuscio, D, Diserens, A C, 2013

机译：勘误到：在Infinium甲基化BeadChip上对胶质母细胞瘤进行MGMT甲基化分析，鉴定出两个与基因沉默和结果相关的不同CpG区域，从而提供了一个预测模型，用于在数据集，肿瘤等级和CIMP状态之间进行比较

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