Arid
DOI10.3389/fonc.2021.714267
M6A Classification Combined With Tumor Microenvironment Immune Characteristics Analysis of Bladder Cancer
Zhu, Huili; Jia, Xiaocan; Wang, Yuping; Song, Zhijuan; Wang, Nana; Yang, Yongli; Shi, Xuezhong
通讯作者Yang, YL ; Shi, XZ (corresponding author), Zhengzhou Univ, Coll Publ Hlth, Dept Epidemiol & Biostat, Zhengzhou, Peoples R China.
来源期刊FRONTIERS IN ONCOLOGY
ISSN2234-943X
出版年2021
卷号11
英文摘要Background Studies have shown that N6-methyl adenosine (m6A) plays an important role in cancer progression; however, the underlying mechanism of m6A modification in tumor microenvironment (TME) cell infiltration of bladder cancer remains unclear. This study aimed to investigate the role of m6A modification in TME cell infiltration of bladder cancer.

Methods The RNA expression profile and clinical data of bladder cancer were obtained from The Cancer Genome Atlas and Gene Expression Omnibus. We assessed the m6A modification patterns of 664 bladder cancer samples based on 20 m6A regulators through unsupervised clustering analysis and systematically linked m6A modification patterns to TME cell infiltration characteristics. Gene ontology and gene set variation analyses were conducted to analyze the underlying mechanism based on the assessment of m6A methylation regulators. Principal component analysis was used to construct the m6A score to quantify m6A modification patterns of bladder cancer.

Results The genetic and expression alterations in m6A regulators were highly heterogeneous between normal and bladder tissues. Three m6A modification patterns were identified. The cell infiltration characteristics were highly consistent with the three immune phenotypes, including immune rejection, immune inflammation, and immune desert. The biological functions of three m6A modification patterns were different. Cox regression analyses revealed that the m6A score was an independent signature with patient prognosis (HR = 1.198, 95% CI: 1.031-1.390). Patients with a low-m6A score were characterized by increased tumor mutation burden, PD-L1 expression, and poorer survival. Patients in the low-m6A score group also showed significant immune responses and clinical benefits in the CTLA-4 immunotherapy cohort (p =0.0069).

Conclusions The m6A methylation modification was related to the formation of TME heterogeneity and complexity. Assessing the m6A modification pattern of individual bladder cancer will improve the understanding of TME infiltration characteristics.

英文关键词m6A bladder cancer mutation burden tumor microenvironment 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:000701304800001
WOS关键词CELL ; DATABASE
WOS类目Oncology
WOS研究方向Oncology
资源类型期刊论文
条目标识符http://119.78.100.177/qdio/handle/2XILL650/363331
作者单位[Zhu, Huili; Jia, Xiaocan; Wang, Yuping; Song, Zhijuan; Wang, Nana; Yang, Yongli; Shi, Xuezhong] Zhengzhou Univ, Coll Publ Hlth, Dept Epidemiol & Biostat, Zhengzhou, Peoples R China
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GB/T 7714
Zhu, Huili,Jia, Xiaocan,Wang, Yuping,et al. M6A Classification Combined With Tumor Microenvironment Immune Characteristics Analysis of Bladder Cancer[J],2021,11.
APA Zhu, Huili.,Jia, Xiaocan.,Wang, Yuping.,Song, Zhijuan.,Wang, Nana.,...&Shi, Xuezhong.(2021).M6A Classification Combined With Tumor Microenvironment Immune Characteristics Analysis of Bladder Cancer.FRONTIERS IN ONCOLOGY,11.
MLA Zhu, Huili,et al."M6A Classification Combined With Tumor Microenvironment Immune Characteristics Analysis of Bladder Cancer".FRONTIERS IN ONCOLOGY 11(2021).
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