m6A regulator-mediated methylation modification patterns and characteristics of immunity and stemness in low-grade glioma

被引：71

作者：

Du, Jianyang ^{[1
]}

Ji, Hang ^{[1
]}

Ma, Shuai ^{[1
]}

Jin, Jiaqi ^{[1
]}

Mi, Shan ^{[1
]}

Hou, Kuiyuan ^{[1
]}

Dong, Jiawei ^{[1
]}

Wang, Fang ^{[1
]}

Zhang, Chaochao ^{[3
]}

Li, Yuan ^{[2
]}

Hu, Shaoshan ^{[1
]}

机构：

[1] Harbin Med Univ, Dept Neurosurg, Affiliated Hosp 2, 157 Baojian Rd, Harbin 150086, Peoples R China

[2] Shandong Univ, Cheeloo Coll Med, Sch Pharmaceut Sci, Dept Pharmacol, Jinan 250012, Shandong, Peoples R China

[3] First Hosp Jilin Univ, Dept Neurosurg, Changchun, Peoples R China

来源：

BRIEFINGS IN BIOINFORMATICS | 2021年 / 22卷 / 05期

基金：

中国国家自然科学基金;

关键词：

m6A; tumor immune microenvironment; stemness; machine learning; immunotherapy; pan-cancer; M(6)A MODIFICATION; IMMUNOTHERAPY; LEUKEMIA; FEATURES; RNAS;

D O I：

10.1093/bib/bbab013

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

m6A RNA methylation is an emerging epigenetic modification, and its potential role in immunity and sternness remains unknown. Based on 17 widely recognized m6A regulators, the m6A modification patterns and corresponding characteristics of immune infiltration and sternness of 1152 low-grade glioma samples were comprehensively analyzed. Machine-learning strategies for constructing m6AScores were trained to quantify the m6A modification patterns of individual samples. Here, we reveal a significant correlation between the multi-omics data of regulators and clinicopathological parameters. We identified two distinct m6A modification patterns (an immune-activated differentiation pattern and an immune-desert dedifferentiation pattern) and four regulatory patterns of m6A methylation on immunity and sternness. We show that the m6AScores can predict the molecular subtype of low-grade glioma, the abundance of immune infiltration, the enrichment of signaling pathways, gene variation and prognosis. The concentration of high immunogenicity and clinical benefits in the low-m6AScore group confirmed the sensitive response to radio-chemotherapy and immunotherapy in patients with high-m6AScore. The results of the pan-cancer analyses illustrate the significant correlation between m6AScore and clinical outcome, the burden of neoepitope, immune infiltration and sternness. The assessment of individual tumor m6A modification patterns will guide us in improving treatment strategies and developing objective diagnostic tools. [GRAPHICS] .

引用

页数：17

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