Comprehensive analyses of m6A regulators and interactive coding and non-coding RNAs across 32 cancer types

Molecular Cancer

Ruyang Zhang¹  Yang Zhao¹  Yi Li²  Zhonghua Liu³  Hongbing Shen⁴  Lijuan Lin⁵  Yue Jiang⁵  Yongyue Wei⁶  Zhibin Hu⁷  Sipeng Shen⁸  Feng Chen⁹ 

[1] Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, 211166, Nanjing, China;China International Cooperation Center of Environment and Human Health, Nanjing Medical University, 211166, Nanjing, Jiangsu, China;Key Laboratory of Biomedical Big Data of Nanjing Medical University, 211166, Nanjing, China;Department of Biostatistics, University of Michigan, 48109, Ann Arbor, MI, USA;Department of Statistics and Actuarial Science, University of Hong Kong, Hong Kong, SAR, China;Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, SPH Building Room 418, 101 Longmian Avenue, 211166, Nanjing, Jiangsu, China;China International Cooperation Center of Environment and Human Health, Nanjing Medical University, 211166, Nanjing, Jiangsu, China;Key Laboratory of Biomedical Big Data of Nanjing Medical University, 211166, Nanjing, China;Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, 211166, Nanjing, China;Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, SPH Building Room 418, 101 Longmian Avenue, 211166, Nanjing, Jiangsu, China;Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, 211166, Nanjing, China;Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, SPH Building Room 418, 101 Longmian Avenue, 211166, Nanjing, Jiangsu, China;Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, 211166, Nanjing, China;China International Cooperation Center of Environment and Human Health, Nanjing Medical University, 211166, Nanjing, Jiangsu, China;State Key Laboratory of Reproductive Medicine, Nanjing Medical University, 211166, Nanjing, China;Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, SPH Building Room 418, 101 Longmian Avenue, 211166, Nanjing, Jiangsu, China;China International Cooperation Center of Environment and Human Health, Nanjing Medical University, 211166, Nanjing, Jiangsu, China;Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, 211166, Nanjing, China;State Key Laboratory of Reproductive Medicine, Nanjing Medical University, 211166, Nanjing, China;Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, SPH Building Room 418, 101 Longmian Avenue, 211166, Nanjing, Jiangsu, China;Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, 211166, Nanjing, China;State Key Laboratory of Reproductive Medicine, Nanjing Medical University, 211166, Nanjing, China;Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, SPH Building Room 418, 101 Longmian Avenue, 211166, Nanjing, Jiangsu, China;Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, 211166, Nanjing, China;China International Cooperation Center of Environment and Human Health, Nanjing Medical University, 211166, Nanjing, Jiangsu, China;Key Laboratory of Biomedical Big Data of Nanjing Medical University, 211166, Nanjing, China;

关键词: N6-Methyladenosine;    Pan-cancer;    Survival outcome;    Multi-omics;   

DOI  :  10.1186/s12943-021-01362-2

来源: Springer

【 摘 要 】

N6-Methyladenosine (m6A) is an RNA modification that interacts with numerous coding and non-coding RNAs and plays important roles in the development of cancers. Nonetheless, the clinical impacts of m6A interactive genes on these cancers largely remain unclear since most studies focus only on a single cancer type. We comprehensively evaluated m6A modification patterns, including 23 m6A regulators and 83 interactive coding and non-coding RNAs among 9,804 pan-cancer samples. We used clustering analysis to identify m6A subtypes and constructed the m6A signature based on an unsupervised approach. We used the signatures to identify potential m6A modification targets across the genome. The prognostic value of one target was further validated in 3,444 samples from six external datasets. We developed three distinct m6A modification subtypes with different tumor microenvironment cell infiltration degrees: immunological, intermediate, and tumor proliferative. They were significantly associated with overall survival in 24 of 27 cancer types. Our constructed individual-level m6A signature was associated with survival, tumor mutation burden, and classical pathways. With the signature, we identified 114 novel genes as potential m6A targets. The gene shared most commonly between cancer types, BCL9L, is an oncogene and interacts with m6A patterns in the Wnt signaling pathway. In conclusion, m6A regulators and their interactive genes impact the outcome of various cancers. Evaluating the m6A subtype and the signature of individual tumors may inform the design of adjuvant treatments.

【 授权许可】

CC BY