Integrating m6A Regulators-Mediated Methylation Modification Models and Tumor Immune Microenvironment Characterization in Caucasian and Chinese Low-Grade Gliomas

Background: As an important epigenetic modification, m6A methylation plays an essential role in post-transcriptional regulation and tumor development. It is urgently needed to comprehensively and rigorously explore the prognostic value of m6A regulators and its association with tumor microenvironmen...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Wangrui Liu, Chuanyu Li, Yuhao Wu, Wenhao Xu, Shuxian Chen, Hailiang Zhang, Haineng Huang, Shuai Zhao, Jian Wang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	m6A low-grade glioma tumor environment immunotherapy prognosis RNA modificatio Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/18aacd7a40e54862b8e5bef5faf19e0a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:18aacd7a40e54862b8e5bef5faf19e0a
record_format	dspace
spelling	oai:doaj.org-article:18aacd7a40e54862b8e5bef5faf19e0a2021-12-01T03:32:39ZIntegrating m6A Regulators-Mediated Methylation Modification Models and Tumor Immune Microenvironment Characterization in Caucasian and Chinese Low-Grade Gliomas2296-634X10.3389/fcell.2021.725764https://doaj.org/article/18aacd7a40e54862b8e5bef5faf19e0a2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.725764/fullhttps://doaj.org/toc/2296-634XBackground: As an important epigenetic modification, m6A methylation plays an essential role in post-transcriptional regulation and tumor development. It is urgently needed to comprehensively and rigorously explore the prognostic value of m6A regulators and its association with tumor microenvironment (TME) infiltration characterization of low-grade glioma (LGG).Methods: Based on the expression of 20 m6A regulatory factors, we comprehensively evaluated the m6A modification patterns of LGG after unsupervised clustering. Subsequent analysis of the differences between these groups was performed to obtain m6A-related genes, then consistent clustering was conducted to generate m6AgeneclusterA and m6AgeneclusterB. A Random Forest and machining learning algorithms were used to reduce dimensionality, identify TME characteristics and predict responses for LGG patients receiving immunotherapies.Results: Evident differential m6A regulators were found in mutation, CNV and TME characteristics of LGG. Based on TCGA and CGGA databases, we identified that m6A regulators clusterA could significantly predict better prognosis (p = 0.00016) which enriched in mTOR signaling pathway, basal transcription factors, accompanied by elevated immune cells infiltration, and decreased IDH and TP53 mutations. We also investigated the distribution of differential genes in m6A regulators clusters which was closely associated with tumor immune microenvironment through three independent cohort comparisons. Next, we established m6Ascore based on previous m6A model, which accurately predicts outcomes in 1089 LGG patients (p < 0.0001) from discovering cohort and 497 LGG patients from testing cohort. Significant TME characteristics, including genome heterogeneity, abidance of immune cells, and clinicopathologic parameters have been found between m6Ascore groups. Importantly, LGG patients with high m6Ascore are confronted with significantly decreased responses to chemotherapies, but benefit more from immunotherapies.Conclusion: In conclusion, this study first demonstrates that m6A modification is crucial participant in tumorigenesis and TME infiltration characterization of LGG based on large-scale cohorts. The m6Ascore provides useful and accurately predict of prognosis and clinical responses to chemotherapy, immunotherapy and therapeutic strategy development for LGG patients.Wangrui LiuWangrui LiuChuanyu LiYuhao WuWenhao XuShuxian ChenHailiang ZhangHaineng HuangShuai ZhaoJian WangFrontiers Media S.A.articlem6Alow-grade gliomatumor environmentimmunotherapyprognosisRNA modificatioBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	m6A low-grade glioma tumor environment immunotherapy prognosis RNA modificatio Biology (General) QH301-705.5
spellingShingle	m6A low-grade glioma tumor environment immunotherapy prognosis RNA modificatio Biology (General) QH301-705.5 Wangrui Liu Wangrui Liu Chuanyu Li Yuhao Wu Wenhao Xu Shuxian Chen Hailiang Zhang Haineng Huang Shuai Zhao Jian Wang Integrating m6A Regulators-Mediated Methylation Modification Models and Tumor Immune Microenvironment Characterization in Caucasian and Chinese Low-Grade Gliomas
description	Background: As an important epigenetic modification, m6A methylation plays an essential role in post-transcriptional regulation and tumor development. It is urgently needed to comprehensively and rigorously explore the prognostic value of m6A regulators and its association with tumor microenvironment (TME) infiltration characterization of low-grade glioma (LGG).Methods: Based on the expression of 20 m6A regulatory factors, we comprehensively evaluated the m6A modification patterns of LGG after unsupervised clustering. Subsequent analysis of the differences between these groups was performed to obtain m6A-related genes, then consistent clustering was conducted to generate m6AgeneclusterA and m6AgeneclusterB. A Random Forest and machining learning algorithms were used to reduce dimensionality, identify TME characteristics and predict responses for LGG patients receiving immunotherapies.Results: Evident differential m6A regulators were found in mutation, CNV and TME characteristics of LGG. Based on TCGA and CGGA databases, we identified that m6A regulators clusterA could significantly predict better prognosis (p = 0.00016) which enriched in mTOR signaling pathway, basal transcription factors, accompanied by elevated immune cells infiltration, and decreased IDH and TP53 mutations. We also investigated the distribution of differential genes in m6A regulators clusters which was closely associated with tumor immune microenvironment through three independent cohort comparisons. Next, we established m6Ascore based on previous m6A model, which accurately predicts outcomes in 1089 LGG patients (p < 0.0001) from discovering cohort and 497 LGG patients from testing cohort. Significant TME characteristics, including genome heterogeneity, abidance of immune cells, and clinicopathologic parameters have been found between m6Ascore groups. Importantly, LGG patients with high m6Ascore are confronted with significantly decreased responses to chemotherapies, but benefit more from immunotherapies.Conclusion: In conclusion, this study first demonstrates that m6A modification is crucial participant in tumorigenesis and TME infiltration characterization of LGG based on large-scale cohorts. The m6Ascore provides useful and accurately predict of prognosis and clinical responses to chemotherapy, immunotherapy and therapeutic strategy development for LGG patients.
format	article
author	Wangrui Liu Wangrui Liu Chuanyu Li Yuhao Wu Wenhao Xu Shuxian Chen Hailiang Zhang Haineng Huang Shuai Zhao Jian Wang
author_facet	Wangrui Liu Wangrui Liu Chuanyu Li Yuhao Wu Wenhao Xu Shuxian Chen Hailiang Zhang Haineng Huang Shuai Zhao Jian Wang
author_sort	Wangrui Liu
title	Integrating m6A Regulators-Mediated Methylation Modification Models and Tumor Immune Microenvironment Characterization in Caucasian and Chinese Low-Grade Gliomas
title_short	Integrating m6A Regulators-Mediated Methylation Modification Models and Tumor Immune Microenvironment Characterization in Caucasian and Chinese Low-Grade Gliomas
title_full	Integrating m6A Regulators-Mediated Methylation Modification Models and Tumor Immune Microenvironment Characterization in Caucasian and Chinese Low-Grade Gliomas
title_fullStr	Integrating m6A Regulators-Mediated Methylation Modification Models and Tumor Immune Microenvironment Characterization in Caucasian and Chinese Low-Grade Gliomas
title_full_unstemmed	Integrating m6A Regulators-Mediated Methylation Modification Models and Tumor Immune Microenvironment Characterization in Caucasian and Chinese Low-Grade Gliomas
title_sort	integrating m6a regulators-mediated methylation modification models and tumor immune microenvironment characterization in caucasian and chinese low-grade gliomas
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/18aacd7a40e54862b8e5bef5faf19e0a
work_keys_str_mv	AT wangruiliu integratingm6aregulatorsmediatedmethylationmodificationmodelsandtumorimmunemicroenvironmentcharacterizationincaucasianandchineselowgradegliomas AT wangruiliu integratingm6aregulatorsmediatedmethylationmodificationmodelsandtumorimmunemicroenvironmentcharacterizationincaucasianandchineselowgradegliomas AT chuanyuli integratingm6aregulatorsmediatedmethylationmodificationmodelsandtumorimmunemicroenvironmentcharacterizationincaucasianandchineselowgradegliomas AT yuhaowu integratingm6aregulatorsmediatedmethylationmodificationmodelsandtumorimmunemicroenvironmentcharacterizationincaucasianandchineselowgradegliomas AT wenhaoxu integratingm6aregulatorsmediatedmethylationmodificationmodelsandtumorimmunemicroenvironmentcharacterizationincaucasianandchineselowgradegliomas AT shuxianchen integratingm6aregulatorsmediatedmethylationmodificationmodelsandtumorimmunemicroenvironmentcharacterizationincaucasianandchineselowgradegliomas AT hailiangzhang integratingm6aregulatorsmediatedmethylationmodificationmodelsandtumorimmunemicroenvironmentcharacterizationincaucasianandchineselowgradegliomas AT hainenghuang integratingm6aregulatorsmediatedmethylationmodificationmodelsandtumorimmunemicroenvironmentcharacterizationincaucasianandchineselowgradegliomas AT shuaizhao integratingm6aregulatorsmediatedmethylationmodificationmodelsandtumorimmunemicroenvironmentcharacterizationincaucasianandchineselowgradegliomas AT jianwang integratingm6aregulatorsmediatedmethylationmodificationmodelsandtumorimmunemicroenvironmentcharacterizationincaucasianandchineselowgradegliomas
_version_	1718405888145883136

Integrating m6A Regulators-Mediated Methylation Modification Models and Tumor Immune Microenvironment Characterization in Caucasian and Chinese Low-Grade Gliomas

Ejemplares similares