干旱区生态环境知识资源中心(Arid): Identification of m(6)A Regulator-Associated Methylation Modification Clusters and Immune Profiles in Melanoma

Arid

DOI	10.3389/fcell.2021.761134
	Identification of m(6)A Regulator-Associated Methylation Modification Clusters and Immune Profiles in Melanoma
	Du, Fengying; Li, Han; Li, Yan; Liu, Yang; Li, Xinyu; Dang, Ningning; Chu, Qingqing; Yan, Jianjun; Fang, Zhen; Wu, Hao; Zhang, Zihao; Zhu, Xingyu; Li, Xiaokang
通讯作者	Li, XK (corresponding author)，Shandong First Med Univ, Cent Hosp, Dept Dermatol, Jinan, 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	RNA N6-methyladenosine (m(6)A) modification in tumorigenesis and progression has been highlighted and discovered in recent years. However, the molecular and clinical implications of m(6)A modification in melanoma tumor microenvironment (TME) and immune infiltration remain largely unknown. Here, we utilized consensus molecular clustering with nonnegative matrix factorization based on the melanoma transcriptomic profiles of 23 m(6)A regulators to determine the m(6)A modification clusters and m(6)A-related gene signature. Three distinct m(6)A modification patterns (m(6)A-C1, C2, and C3), which are characterized by specific m(6)A regulator expression, survival outcomes, and biological pathways, were identified in more than 1,000 melanoma samples. The immune profile analyses showed that these three m(6)A modification subtypes were highly consistent with the three known immune phenotypes: immune-desert (C1), immune-excluded (C2), and immune-inflamed (C3). Tumor digital cytometry (CIBERSORT, ssGSEA) algorithm revealed an upregulated infiltration of CD8(+) T cell and NK cell in m(6)A-C3 subtype. An m(6)A scoring scheme calculated by principal component of m(6)A signatures stratified melanoma patients into high- and low-m(6)sig score subgroups; a high score was significantly associated with prolonged survival and enhanced immune infiltration. Furthermore, fewer somatic copy number alternations (SCNA) and PD-L1 expression were found in patients with high m(6)Sig score. In addition, patients with high m(6)Sig score demonstrated marked immune responses and durable clinical benefits in two independent immunotherapy cohorts. Overall, this study indicated that m(6)A modification is involved in melanoma tumor microenvironment immune regulation and contributes to formation of tumor immunogenicity. Comprehensive evaluation of the m(6)A modification pattern of individual tumors will provide more insights into molecular mechanisms of TME characterization and promote more effective personalized biotherapy strategies.
英文关键词	skin cutaneous melanoma methylation of N6 adenosine modification tumor microenvironment immune profiles immunotherapy
类型	Article
语种	英语
开放获取类型	Green Published, gold
收录类别	SCI-E
WOS记录号	WOS:000739056400001
WOS关键词	CANCER ; MICROENVIRONMENT ; BLOCKADE ; IMMUNOPHENOTYPE ; SIGNATURE
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/2XILL650/375663
作者单位	[Du, Fengying; Li, Xiaokang] Shandong First Med Univ, Cent Hosp, Dept Dermatol, Jinan, Peoples R China; [Du, Fengying; Liu, Yang; Wu, Hao; Zhang, Zihao] Shandong Univ, Shandong Prov Hosp, Cheeloo Coll Med, Dept Gastroenterol Surg, Jinan, Peoples R China; [Du, Fengying; Liu, Yang; Wu, Hao; Zhang, Zihao; Zhu, Xingyu] Shandong First Med Univ & Shandong Acad Med Sci, Med Sci & Technol Innovat Ctr, Jinan, Peoples R China; [Li, Han] Shandong First Med Univ, Affiliated Hosp 1, Dept Gastroenterol Surg, Jinan, Peoples R China; [Li, Yan] Shandong Publ Hlth Clin Ctr, Dept Resp & Crit Care, Jinan, Peoples R China; [Li, Xinyu] Shandong First Med Univ, Shandong Prov Hosp, Dept Oncol, Jinan, Peoples R China; [Dang, Ningning] Shandong First Med Univ, Shandong Prov Hosp, Dept Dermatol, Jinan, Peoples R China; [Chu, Qingqing] Matern & Child Hlth Care Zaozhuang, Outpatient Podiat Rehabil, Zaozhuang, Peoples R China; [Yan, Jianjun] Shandong Univ, Qilu Hosp, Dept Dermatol, Jinan, Peoples R China; [Fang, Zhen] Capital Med Univ...
推荐引用方式 GB/T 7714	Du, Fengying,Li, Han,Li, Yan,et al. Identification of m(6)A Regulator-Associated Methylation Modification Clusters and Immune Profiles in Melanoma[J],2021,9.
APA	Du, Fengying.,Li, Han.,Li, Yan.,Liu, Yang.,Li, Xinyu.,...&Li, Xiaokang.(2021).Identification of m(6)A Regulator-Associated Methylation Modification Clusters and Immune Profiles in Melanoma.FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY,9.
MLA	Du, Fengying,et al."Identification of m(6)A Regulator-Associated Methylation Modification Clusters and Immune Profiles in Melanoma".FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY 9(2021).