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胶质瘤中mA特征与肿瘤免疫微环境的预后分析及验证

Prognosis Analysis and Validation of mA Signature and Tumor Immune Microenvironment in Glioma.

作者信息

Lin Shaojian, Xu Houshi, Zhang Anke, Ni Yunjia, Xu Yuanzhi, Meng Tong, Wang Mingjie, Lou Meiqing

机构信息

Department of Neurosurgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

School of Medicine, Tongji University, Shanghai, China.

出版信息

Front Oncol. 2020 Oct 5;10:541401. doi: 10.3389/fonc.2020.541401. eCollection 2020.

Abstract

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 mA 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 mA 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 mA cluster 1/2 groups were utilized for the hub genes, and four genes ( 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 and 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 and may serve as potential biomarkers for prognosis of glioma.

摘要

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%。几种关键的分子特征已成为预后生物标志物,这表明当前胶质瘤分类方法仍有改进空间。为了构建更准确的预测模型并识别潜在的预后生物标志物,我们探索了来自TCGA-GBM和TCGA-LGG的665例胶质瘤中差异表达的m⁶A RNA甲基化调节因子。对m⁶A RNA甲基化调节因子进行一致性聚类,在聚类1中鉴定出两个预后较差且WHO分级较高的胶质瘤亚组。进一步的卡方检验表明,聚类1中免疫浸润显著富集,表明m⁶A调节因子与免疫浸润密切相关。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)以及最小绝对收缩和选择算子(LASSO),对高/低免疫浸润和m⁶A聚类1/2组之间的枢纽基因进行分析,鉴定出四个基因作为预后生物标志物。此外,基于这四个基因构建了一个预后模型,该模型对胶质瘤患者的总生存期(OS)具有良好的预测能力和适用性(在TCGA和中国胶质瘤基因组图谱(CGGA)中,ROC曲线下面积分别达到0.80(0.76 - 0.83)和0.72(0.68 - 0.76))。此外,我们还发现[具体基因1]和[具体基因2]在人类蛋白质图谱数据库的高级别胶质瘤中高表达,且它们在胶质瘤组织样本中均与m⁶A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。[具体基因1]和[具体基因2]可能作为胶质瘤预后的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e42b/7571468/7d98146089b3/fonc-10-541401-g0001.jpg

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