干旱区生态环境知识资源中心(Arid): m(6)A regulator-mediated methylation modification patterns and tumor microenvironment infiltration characterization in gastric cancer

Arid

DOI	10.1186/s12943-020-01170-0
	m(6)A regulator-mediated methylation modification patterns and tumor microenvironment infiltration characterization in gastric cancer
	Zhang, Bo 1,2; Wu, Qiong 1,2; Li, Ben 3; Wang, Defeng 1; Wang, Lei 4; Zhou, You Lang 1
通讯作者	Wang, Lei ; Zhou, You Lang
来源期刊	MOLECULAR CANCER
EISSN	1476-4598
出版年	2020
卷号	19 期号:1
英文摘要	Background The epigenetic regulation of immune response has been demonstrated in recent studies. Nonetheless, potential roles of RNA N6-methyladenosine (m(6)A) modification in tumor microenvironment (TME) cell infiltration remain unknown. Methods We comprehensively evaluated the m(6)A modification patterns of 1938 gastric cancer samples based on 21 m(6)A regulators, and systematically correlated these modification patterns with TME cell-infiltrating characteristics. The m6Ascore was constructed to quantify m(6)A modification patterns of individual tumors using principal component analysis algorithms. Results Three distinct m(6)A modification patterns were determined. The TME cell-infiltrating characteristics under these three patterns were highly consistent with the three immune phenotypes of tumors including immune-excluded, immune-inflamed and immune-desert phenotypes. We demonstrated the evaluation of m(6)A modification patterns within individual tumors could predict stages of tumor inflammation, subtypes, TME stromal activity, genetic variation, and patient prognosis. Low m6Ascore, characterized by increased mutation burden and activation of immunity, indicated an inflamed TME phenotype, with 69.4% 5-year survival. Activation of stroma and lack of effective immune infiltration were observed in the high m6Ascore subtype, indicating a non-inflamed and immune-exclusion TME phenotype, with poorer survival. Low m6Ascore was also linked to increased neoantigen load and enhanced response to anti-PD-1/L1 immunotherapy. Two immunotherapy cohorts confirmed patients with lower m6Ascore demonstrated significant therapeutic advantages and clinical benefits. Conclusions This work revealed the m(6)A modification played a nonnegligible role in formation of TME diversity and complexity. Evaluating the m(6)A modification pattern of individual tumor will contribute to enhancing our cognition of TME infiltration characterization and guiding more effective immunotherapy strategies.
英文关键词	m(6)A Tumor microenvironment Stroma Immunotherapy Mutation burden
类型	Article
语种	英语
国家	Peoples R China
开放获取类型	gold, Green Published
收录类别	SCI-E
WOS记录号	WOS:000519935600001
WOS关键词	RNA METHYLATION ; EXPRESSION ; CELLS ; EXCLUSION ; BLOCKADE ; IMMUNITY
WOS类目	Biochemistry & Molecular Biology ; Oncology
WOS研究方向	Biochemistry & Molecular Biology ; Oncology
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/315188
作者单位	1.Nantong Univ, Res Ctr Clin Med, Affiliated Hosp, Nantong 226001, Jiangsu, Peoples R China; 2.Nantong Univ, Med Sch, Nantong 226001, Jiangsu, Peoples R China; 3.Nantong Univ, Dept Cardiothorac Surg, Affiliated Hosp, Nantong 226001, Jiangsu, Peoples R China; 4.Shanghai Jiao Tong Univ, Sch Life Sci & Biotechnol, State Key Lab Microbial Metab, Shanghai 200240, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Bo,Wu, Qiong,Li, Ben,et al. m(6)A regulator-mediated methylation modification patterns and tumor microenvironment infiltration characterization in gastric cancer[J],2020,19(1).
APA	Zhang, Bo,Wu, Qiong,Li, Ben,Wang, Defeng,Wang, Lei,&Zhou, You Lang.(2020).m(6)A regulator-mediated methylation modification patterns and tumor microenvironment infiltration characterization in gastric cancer.MOLECULAR CANCER,19(1).
MLA	Zhang, Bo,et al."m(6)A regulator-mediated methylation modification patterns and tumor microenvironment infiltration characterization in gastric cancer".MOLECULAR CANCER 19.1(2020).