Exploring the role of m6A methylation regulators in glioblastoma multiforme and their impact on the tumor immune microenvironment

doi:10.1096/fj.202301343

科研成果详情

题名	Exploring the role of m6A methylation regulators in glioblastoma multiforme and their impact on the tumor immune microenvironment
作者	Deng, Xinpeng 1; Sun, Xiaoke 2; Hu, Ziliang 1; Wu, Yiwen 1; Zhou, Chenhui 1; Sun, Jie 1; Gao, Xiang 1; Huang, Yi 1,3
发表日期	2023-09
发表期刊	FASEB journal : official publication of the Federation of American Societies for Experimental Biology 影响因子和分区
语种	英语
原始文献类型	Journal Article ; Research Support, Non-U.S. Gov't
关键词	N6-methyladenosine methylation PD-1 PD-L1 RNA methylation glioblastoma multiforme immune infiltrates prognosis
其他关键词	CELL LUNG-CANCER ; EXPRESSION ; PROLIFERATION ; N-6-METHYLADENOSINE ; SUPPRESSES ; INVASION
摘要	Although the role of N6-Methyladenosine (m6A) methylation factors has been established in multiple cancer types, its involvement in glioblastoma multiforme (GBM) remains limited. This study aims to explore the involvement of m6A regulators in GBM and examine their association with the tumor immune microenvironment (TIME). A comprehensive set of 24 candidate m6A RNA regulators was procured. Consensus clustering was performed based on these regulators to identify distinct GBM clusters. PD-L1 and PD-1 levels, immune cell infiltration, and immune scores were evaluated between two clusters. Prognostic signatures and correlation analysis with TIME were analyzed using Lasso and Spearman's analysis. GBM tissue was collected to verify the correlations. Eighteen m6A regulators (WTAP, YTHDF2, HNRNPC, CAPRIN1, YTHDF3, METTL14, GNL3, ZCCHC4, HNRNPD, YTHDF1, RBM15, PCIF1, RBM27, KIAA1429, MSI2, FTO, ALKBH5, and METTL3), PD-L1, and PD-1 were significantly upregulated in GBM tissue. These regulators were divided into two distinct molecular subtypes (clusters 1 and 2). Cluster 2 exhibited a significant increase in immune score, monocytes, M1 macrophages, activated mast cells, and eosinophils. HNRNPC, YWHAG, and ALKBH5 were significantly associated with TIME and positively correlated with PD-L1. Immune cell invasiveness profiles dynamically changed with copy number changes of these three m6A regulators. Finally, YWHAG and ALKBH5 were found to be independent prognostic indicators of GBM through risk analysis and were experimentally verified with clinical samples. YWHAG and ALKBH5 may be used as prognostic markers for patients with GBM. m6A methylation regulators may play an important role in regulating PD-L1/PD-1 expression and immune infiltration, thus having a significant impact on GBM TIME.
资助项目	Science and Technology Innovation 2025 Major Project of Ningbo [2022Z125]; Ningbo Medical and Health Brand Discipline [PPXK2018-04]; Ningbo Top Medical and Health Research Program [2022020304]; Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province [2022E10026]
出版者	WILEY
ISSN	0892-6638
EISSN	1530-6860
卷号	37 期号:9
DOI	10.1096/fj.202301343
页数	14
WOS类目	Biochemistry & Molecular Biology ; Biology ; Cell Biology
WOS研究方向	Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics ; Cell Biology
WOS记录号	WOS:001052595600001
收录类别	PUBMED ; SCIE ; SCOPUS
URL	查看原文
PubMed ID	37606566
SCOPUSEID	2-s2.0-85168538722
通讯作者地址	[Gao, Xiang]Department of Neurosurgery,The First Affiliated Hospital of Ningbo University,Liuting Street 59, Zhejiang,Ningbo,315000,China ; [Huang, Yi]Department of Neurosurgery,The First Affiliated Hospital of Ningbo University,Ningbo,China
Scopus学科分类	Biotechnology;Biochemistry;Molecular Biology;Genetics
TOP期刊	TOP期刊
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/182475
专题	其他_附属慈溪医院（慈溪市人民医院）
通讯作者	Gao, Xiang; Huang, Yi
作者单位	1.Department of Neurosurgery,The First Affiliated Hospital of Ningbo University,Ningbo,China; 2.Affiliated Cixi Hospital,Wenzhou Medical University,Ningbo,China; 3.Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province,Ningbo,China
推荐引用方式 GB/T 7714	Deng, Xinpeng,Sun, Xiaoke,Hu, Ziliang,et al. Exploring the role of m6A methylation regulators in glioblastoma multiforme and their impact on the tumor immune microenvironment[J]. FASEB journal : official publication of the Federation of American Societies for Experimental Biology,2023,37(9).
APA	Deng, Xinpeng., Sun, Xiaoke., Hu, Ziliang., Wu, Yiwen., Zhou, Chenhui., ... & Huang, Yi. (2023). Exploring the role of m6A methylation regulators in glioblastoma multiforme and their impact on the tumor immune microenvironment. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 37(9).
MLA	Deng, Xinpeng,et al."Exploring the role of m6A methylation regulators in glioblastoma multiforme and their impact on the tumor immune microenvironment".FASEB journal : official publication of the Federation of American Societies for Experimental Biology 37.9(2023).