干旱区生态环境知识资源中心(Arid): m6A Regulator-Associated Modification Patterns and Immune Infiltration of the Tumor Microenvironment in Hepatocarcinoma

Arid

DOI	10.3389/fcell.2021.687756
	m6A Regulator-Associated Modification Patterns and Immune Infiltration of the Tumor Microenvironment in Hepatocarcinoma
	Li, Jianhao; Wang, Weiwei; Zhou, Yubing; Liu, Liwen; Zhang, Guizhen; Guan, Kelei; Cui, Xichun; Liu, Xin; Huang, Maoxin; Cui, Guangying; Sun, Ranran
通讯作者	Cui, GY ; Sun, RR (corresponding author), Zhengzhou Univ, Precis Med Ctr, Affiliated Hosp 1, Zhengzhou, Peoples R China. ; Cui, GY ; Sun, RR (corresponding author), Zhengzhou Univ, Key Lab Clin Med, Affiliated Hosp 1, Zhengzhou, Peoples R China.
来源期刊	FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
ISSN	2296-634X
出版年	2021
卷号	9
英文摘要	Background: Immunotherapy elicits durable responses in many tumors. Nevertheless, the positive response to immunotherapy always depends on the dynamic interactions between the tumor cells and infiltrating lymphocytes in the tumor microenvironment (TME). Currently, the application of immunotherapy in hepatocellular carcinoma (HCC) has achieved limited success. The ectopic modification of N6-methyladenosine (m6A) is a common feature in multiple tumors. However, the relationship between m6A modification with HCC clinical features, prognosis, immune cell infiltration, and immunotherapy efficacy remains unclear. Materials and Methods: Here, we comprehensively evaluated m6A modification clusters based on 22 m6A regulators and systematically explored the relationship between m6A modification with tumor progression, prognosis, and immune cell infiltration characteristics. The m6Ascore was calculated by principal component analysis to quantify the m6A modifications of individual patients. Key regulators involved in immunoregulation in HCC were identified using immunohistochemistry and immunofluorescence. Results: Three distinct m6A modification clusters were identified. The m6A clusters were significantly associated with clinical features, prognosis, and immune cell infiltration. The three clusters were highly consistent with the three tumor immune phenotypes, i.e., immune-excluded, immune-inflamed, and immune-desert. Comprehensive bioinformatics analysis revealed that high m6Ascore was closely associated with tumor progression, poor prognosis, and immunotherapy non-response. m6A regulators were dysregulated in HCC tissues. Hence, they play a role as predictors of poor prognosis. Tissue microarray demonstrated that overexpressed YTHDF1 was associated with low CD3(+) and CD8(+) T cell infiltration in HCC. Conclusion: Our findings demonstrate that m6A modification patterns play a crucial role in the tumor immune microenvironment and the prognosis of HCC. High YTHDF1 expression is closely associated with low CD3(+) and CD8(+) T cell infiltration in HCC.
英文关键词	N6-methyladenosine hepatocellular carcinoma tumor microenvironment prognosis immune infiltration
类型	Article
语种	英语
开放获取类型	gold, Green Published
收录类别	SCI-E
WOS记录号	WOS:000673967200001
WOS关键词	HEPATOCELLULAR-CARCINOMA ; METHYLTRANSFERASE METTL3 ; METHYLATION ; CANCER
WOS类目	Cell Biology ; Developmental Biology
WOS研究方向	Cell Biology ; Developmental Biology
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/363278
作者单位	[Li, Jianhao; Liu, Liwen; Zhang, Guizhen; Liu, Xin; Cui, Guangying; Sun, Ranran] Zhengzhou Univ, Precis Med Ctr, Affiliated Hosp 1, Zhengzhou, Peoples R China; [Li, Jianhao; Zhou, Yubing; Liu, Liwen; Zhang, Guizhen; Cui, Xichun; Liu, Xin; Cui, Guangying; Sun, Ranran] Zhengzhou Univ, Key Lab Clin Med, Affiliated Hosp 1, Zhengzhou, Peoples R China; [Wang, Weiwei] Zhengzhou Univ, Dept Pathol, Affiliated Hosp 1, Zhengzhou, Peoples R China; [Zhou, Yubing; Guan, Kelei] Zhengzhou Univ, Dept Pharm, Affiliated Hosp 1, Zhengzhou, Peoples R China; [Huang, Maoxin] Zhengzhou Univ, Dept Dermatol, Affiliated Hosp 1, Zhengzhou, Peoples R China
推荐引用方式 GB/T 7714	Li, Jianhao,Wang, Weiwei,Zhou, Yubing,et al. m6A Regulator-Associated Modification Patterns and Immune Infiltration of the Tumor Microenvironment in Hepatocarcinoma[J],2021,9.
APA	Li, Jianhao.,Wang, Weiwei.,Zhou, Yubing.,Liu, Liwen.,Zhang, Guizhen.,...&Sun, Ranran.(2021).m6A Regulator-Associated Modification Patterns and Immune Infiltration of the Tumor Microenvironment in Hepatocarcinoma.FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY,9.
MLA	Li, Jianhao,et al."m6A Regulator-Associated Modification Patterns and Immune Infiltration of the Tumor Microenvironment in Hepatocarcinoma".FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY 9(2021).