Prognosis Analysis and Validation of m(6)A Signature and Tumor Immune Microenvironment in Glioma.
Prognosis Analysis and Validation of m(6)A Signature and Tumor Immune Microenvironment in Glioma.
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胶质瘤中 m(6)A 特征和肿瘤免疫微环境的预后分析和验证
DOI：
10.3389/fonc.2020.541401
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发表时间：
2020
影响因子：
4.7
通讯作者：
Lou M
中科院分区：
文献类型：
--
作者：
Lin S;Xu H;Zhang A;Ni Y;Xu Y;Meng T;Wang M;Lou M
胶质瘤是最典型的颅内肿瘤之一，约占所有脑恶性肿瘤的80%。几个关键的分子标记已经成为预后生物标志物，这表明在目前的胶质瘤分类方法的改进空间。为了建立一个更准确的预测模型，并确定潜在的肿瘤生物标志物，我们探讨了665例TCGA-GBM和TCGA-LGG胶质瘤中差异表达的m6 A RNA甲基化调控因子。共识聚类应用于m6 A RNA甲基化调节剂，并确定了两个胶质瘤亚组，其预后较差，并且在聚类1中具有较高的WHO分类等级。进一步的卡方检验表明，免疫浸润在簇1中显著富集，表明m6 A调节剂与免疫浸润之间的密切关系。为了探索潜在的生物标志物，利用加权基因共表达网络分析（WGCNA），沿着最小绝对收缩和选择算子（LASSO），在高/低免疫浸润和m6 A簇1/2组之间用于枢纽基因，并且鉴定出4个基因（TAGLN 2、PDPN、TIMP 1、EMP 3）作为预后生物标志物。此外，基于这4个基因构建的预测模型对胶质瘤患者的总生存期（OS）具有较好的预测性和适用性（TCGA和中国胶质瘤基因组图谱（CGGA）的ROC曲线下面积分别为0.80（0.76-0.83）和0.72（0.68-0.76））。此外，我们还发现PDPN和TIMP 1在人类蛋白质图谱数据库中的高级别胶质瘤中高表达，并且两者都与胶质瘤组织样本中的m6 A和免疫细胞标志物相关。总之，我们构建了一个新的预后模型，为胶质瘤预后提供了新的见解。PDPN和TIMP 1可作为判断胶质瘤预后的潜在生物标志物。
Glioma is one of the most typical intracranial tumors, comprising about 80% of all brain malignancies. Several key molecular signatures have emerged as prognostic biomarkers, which indicate room for improvement in the current approach to glioma classification. In order to construct a more veracious prediction model and identify the potential prognosis-biomarker, we explore the differential expressed m6A RNA methylation regulators in 665 gliomas from TCGA-GBM and TCGA-LGG. Consensus clustering was applied to the m6A RNA methylation regulators, and two glioma subgroups were identified with a poorer prognosis and a higher grade of WHO classification in cluster 1. The further chi-squared test indicated that the immune infiltration was significantly enriched in cluster 1, indicating a close relation between m6A regulators and immune infiltration. In order to explore the potential biomarkers, the weighted gene co-expression network analysis (WGCNA), along with Least absolute shrinkage and selection operator (LASSO), between high/low immune infiltration and m6A cluster 1/2 groups were utilized for the hub genes, and four genes (TAGLN2, PDPN, TIMP1, EMP3) were identified as prognostic biomarkers. Besides, a prognostic model was constructed based on the four genes with a good prediction and applicability for the overall survival (OS) of glioma patients (the area under the curve of ROC achieved 0.80 (0.76–0.83) and 0.72 (0.68–0.76) in TCGA and Chinese Glioma Genome Atlas (CGGA), respectively). Moreover, we also found PDPN and TIMP1 were highly expressed in high-grade glioma from The Human Protein Atlas database and both of them were correlated with m6A and immune cell marker in glioma tissue samples. In conclusion, we construct a novel prognostic model which provides new insights into glioma prognosis. The PDPN and TIMP1 may serve as potential biomarkers for prognosis of glioma.
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影响因子：
4.6
作者：
Bresson, Laura;Faraldo, Marisa M.;Deugnier, Marie-Ange
通讯作者：
Deugnier, Marie-Ange
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通讯作者：
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