干旱区生态环境知识资源中心(Arid): m(6)A regulator-based methylation modification patterns characterized by distinct tumor microenvironment immune profiles in colon cancer

Arid

DOI	10.7150/thno.52717
	m(6)A regulator-based methylation modification patterns characterized by distinct tumor microenvironment immune profiles in colon cancer
	Chong, Wei; Shang, Liang; Liu, Jin; Fang, Zhen; Du, Fengying; Wu, Hao; Liu, Yang; Wang, Zhe; Chen, Yang; Jia, Shengtao; Chen, Liming; Li, Leping; Chen, Hao
通讯作者	Li, LP (corresponding author), Shandong First Med Univ, Shandong Prov Hosp, Dept Gastrointestinal Surg, Jinan 250021, Shandong, Peoples R China. ; Chen, H (corresponding author), Shandong Univ, Qilu Hosp, Clin Res Ctr, Clin Epidemiol Unit, Jinan 250021, Shandong, Peoples R China.
来源期刊	THERANOSTICS
ISSN	1838-7640
出版年	2021
卷号	11 期号:5 页码:2201-2217
英文摘要	Recent studies have highlighted the biological significance of RNA N-6-methyladenosine (m(6)A) modification in tumorigenicity and progression. However, it remains unclear whether m(6)A modifications also have potential roles in immune regulation and tumor microenvironment (TME) formation. Methods: In this study, we curated 23 m(6)A regulators and performed consensus molecular subtyping with NMF algorithm to determine m(6)A modification patterns and the m(6)A-related gene signature in colon cancer (CC). The ssGSEA and CIBERSORT algorithms were employed to quantify the relative infiltration levels of various immune cell subsets. An PCA algorithm based m(6)Sig scoring scheme was used to evaluate the m(6)A modification patterns of individual tumors with an immune response. Results: Three distinct m(6)A modification patterns were identified among 1307 CC samples, which were also associated with different clinical outcomes and biological pathways. The TME characterization revealed that the identified m(6)A patterns were highly consistent with three known immune profiles: immune-inflamed, immune-excluded, and immune-desert, respectively. Based on the m(6)Sig score, which was extracted from the m(6)A-related signature genes, CC patients can be divided into high and low score subgroups. Patients with lower m(6)Sig score was characterized by prolonged survival time and enhanced immune infiltration. Further analysis indicated that lower m(6)Sig score also correlated with greater tumor mutation loads, PD-L1 expression, and higher mutation rates in SMGs (e.g., PIK3CA and SMAD4). In addition, patients with lower m(6)Sig scores showed a better immune responses and durable clinical benefits in three independent immunotherapy cohorts. Conclusions: This study highlights that m(6)A modification is significantly associated with TME diversity and complexity. Quantitatively evaluating the m(6)A modification patterns of individual tumors will strengthen our understanding of TME characteristics and promote more effective immunotherapy strategies.
英文关键词	Colon cancer m(6)A modification Tumor microenvironment Immune profiles Immunotherapy
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:000600556000015
WOS关键词	COLORECTAL-CANCER ; CHECKPOINT BLOCKADE ; IMMUNOPHENOTYPE ; SIGNATURE ; HALLMARKS ; CELLS
WOS类目	Medicine, Research & Experimental
WOS研究方向	Research & Experimental Medicine
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/348249
作者单位	[Chong, Wei; Shang, Liang; Li, Leping] Shandong First Med Univ, Shandong Prov Hosp, Dept Gastrointestinal Surg, Jinan 250021, Shandong, Peoples R China; [Chong, Wei; Shang, Liang; Fang, Zhen; Du, Fengying; Wu, Hao; Liu, Yang; Li, Leping] Shandong Univ, Shandong Prov Hosp, Cheeloo Coll Med, Dept Gastrointestinal Surg, Jinan 250021, Shandong, Peoples R China; [Chong, Wei; Shang, Liang; Fang, Zhen; Du, Fengying; Wu, Hao; Liu, Yang; Li, Leping] Shandong Prov Hosp, Key Lab Engn Shandong Prov, Jinan 250021, Shandong, Peoples R China; [Liu, Jin] Shandong Prov Hosp, Dept Gastroenterol, Key Lab Engn Shandong Prov, Jinan 250021, Shandong, Peoples R China; [Wang, Zhe] Tianjin Sino US Diagnost Co Ltd, Tianjin, Peoples R China; [Chen, Yang] Tianjin Med Univ Canc Inst & Hosp, Natl Clin Res Ctr Canc, Dept Radiat Oncol, Tianjin, Peoples R China; [Chen, Yang] Key Lab Canc Prevent & Therapy, Tianjin, Peoples R China; [Chen, Yang] Tianjins Clin Res Ctr Canc, Tianjin, Peoples R China; [Jia, Shengtao] Tianjin Med Univ Canc In...
推荐引用方式 GB/T 7714	Chong, Wei,Shang, Liang,Liu, Jin,et al. m(6)A regulator-based methylation modification patterns characterized by distinct tumor microenvironment immune profiles in colon cancer[J],2021,11(5):2201-2217.
APA	Chong, Wei.,Shang, Liang.,Liu, Jin.,Fang, Zhen.,Du, Fengying.,...&Chen, Hao.(2021).m(6)A regulator-based methylation modification patterns characterized by distinct tumor microenvironment immune profiles in colon cancer.THERANOSTICS,11(5),2201-2217.
MLA	Chong, Wei,et al."m(6)A regulator-based methylation modification patterns characterized by distinct tumor microenvironment immune profiles in colon cancer".THERANOSTICS 11.5(2021):2201-2217.