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RNA N6-甲基腺苷调节剂介导的胶质母细胞瘤甲基化修饰模式及免疫浸润特征

RNA N6-Methyladenosine Regulator-Mediated Methylation Modifications Pattern and Immune Infiltration Features in Glioblastoma.

作者信息

Pan Yimin, Xiao Kai, Li Yue, Li Yuzhe, Liu Qing

机构信息

Department of Neurosurgery in Xiangya Hospital, Central South University, Changsha, China.

出版信息

Front Oncol. 2021 Feb 25;11:632934. doi: 10.3389/fonc.2021.632934. eCollection 2021.

Abstract

Glioblastoma (GBM) is a group of intracranial neoplasms with intra-tumoral heterogeneity. RNA N6-methyladenosine (mA) methylation modification reportedly plays roles in immune response. The relationship between the mA modification pattern and immune cell infiltration in GBM remains unknown. Utilizing expression data of GBM patients, we thoroughly explored the potential mA modification pattern and mA-related signatures based on 21 regulators. Thereafter, the mA methylation modification-based prognostic assessment pipeline (MPAP) was constructed to quantitatively assess GBM patients' clinical prognosis combining the Robustness and LASSO regression. Single-sample gene-set enrichment analysis (ssGSEA) was used to estimate the specific immune cell infiltration level. We identified two diverse clusters with diverse mA modification characteristics. Based on differentially expressed genes (DEGs) within two clusters, mA-related signatures were identified to establish the MPAP, which can be used to quantitatively forecast the prognosis of GBM patients. In addition, the relationship between 21 mA regulators and specific immune cell infiltration was demonstrated in our study and the mA regulator ELAVL1 was determined to play an important role in the anticancer response to PD-L1 therapy. Our findings indicated the relationship between mA methylation modification patterns and tumor microenvironment immune cell infiltration, through which we could comprehensively understand resistance to multiple therapies in GBM, as well as accomplish precise risk stratification according to mA-related signatures.

摘要

胶质母细胞瘤(GBM)是一组具有肿瘤内异质性的颅内肿瘤。据报道,RNA N6-甲基腺苷(m⁶A)甲基化修饰在免疫反应中发挥作用。GBM中m⁶A修饰模式与免疫细胞浸润之间的关系尚不清楚。利用GBM患者的表达数据,我们基于21种调节因子深入探索了潜在的m⁶A修饰模式和m⁶A相关特征。此后,构建了基于m⁶A甲基化修饰的预后评估流程(MPAP),结合稳健性和LASSO回归定量评估GBM患者的临床预后。采用单样本基因集富集分析(ssGSEA)来估计特定免疫细胞浸润水平。我们识别出了具有不同m⁶A修饰特征的两个不同簇。基于两个簇内的差异表达基因(DEG),识别出m⁶A相关特征以建立MPAP,其可用于定量预测GBM患者的预后。此外,我们的研究证明了21种m⁶A调节因子与特定免疫细胞浸润之间的关系,并且确定m⁶A调节因子ELAVL1在对PD-L1治疗的抗癌反应中起重要作用。我们的研究结果表明了m⁶A甲基化修饰模式与肿瘤微环境免疫细胞浸润之间的关系,通过这一关系我们可以全面了解GBM对多种治疗的耐药性,以及根据m⁶A相关特征完成精确的风险分层。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bb2/7947873/7da9a66dbaaa/fonc-11-632934-g001.jpg

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