Comprehensive characterization of tumor microenvironment and m6A RNA methylation regulators and its effects on PD-L1 and immune infiltrates in cervical cancer

被引:25
|
作者
Ji, Huihui [1 ]
Zhang, Jian-an [1 ]
Liu, Hejing [1 ]
Li, Kehan [1 ]
Wang, Zhi-wei [1 ]
Zhu, Xueqiong [1 ]
机构
[1] Wenzhou Med Univ, Affiliated Hosp 2, Ctr Uterine Canc Diag & Therapy Res Zhejiang Prov, Dept Obstet & Gynecol, Wenzhou, Peoples R China
来源
FRONTIERS IN IMMUNOLOGY | 2022年 / 13卷
基金
中国国家自然科学基金;
关键词
cervical cancer; M6A; TME; PD-1; PD-L1; TIME; MESSENGER-RNA; CELLS;
D O I
10.3389/fimmu.2022.976107
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Understanding the role of N6-adenosine methylation (m6A) in the tumor microenvironment (TME) is important since it can contribute to tumor development. However, the research investigating the association between m6A and TME and cervical cancer is still in its early stages. The aim of this study was to discover the possible relationship between m6A RNA methylation regulators, TME, PD-L1 expression levels, and immune infiltration in cervical cancer. We gathered RNA-seq transcriptome data and clinical information from cervical cancer patients using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. To begin, researchers assessed the differences in m6A regulatory factor expression levels between cervical cancer and normal tissues. Clustering analysis was adapted to assess PD-L1 expression, immunological score, immune cell infiltration, TME, and probable pathways in cervical cancer samples. The majority of m6A regulators were found to be considerably overexpressed in cervical cancer tissues. Using consensus clustering of 21 m6A regulators, we identified two subtypes (clusters 1/2) of cervical cancer, and we found that WHO stage and grade were associated with the subtypes. PD-L1 expression increased dramatically in cervical cancer tissues and was significantly linked to ALKBH5, FTO, METTL3, RBM15B, YTHDF1, YTHDF3, and ZC3H13 expression levels. Plasma cells and regulatory T cells (Tregs) were considerably elevated in cluster 2. Cluster 1 is involved in numerous signature pathways, including basal transcription factors, cell cycle, RNA degradation, and the spliceosome. The prognostic signature-based riskscore (METTL16, YTHDF1, and ZC3H13) was found to be an independent prognostic indicator of cervical cancer. The tumor immune microenvironment (TIME) was linked to m6A methylation regulators, and changes in their copy number will affect the quantity of tumor-infiltrating immune cells dynamically. Overall, our research discovered a powerful predictive signature based on m6A RNA methylation regulators. This signature correctly predicted the prognosis of cervical cancer patients. The m6A methylation regulator could be a critical mediator of PD-L1 expression and immune cell infiltration, and it could have a significant impact on the TIME of cervical cancer.
引用
收藏
页数:15
相关论文
共 50 条
  • [41] CMTM6 and PD-L1 coexpression is associated with an active immune microenvironment and a favorable prognosis in colorectal cancer
    Peng, Qi-Hua
    Wang, Chun-Hua
    Chen, Hong-Min
    Zhang, Rong-Xin
    Pan, Zhi-Zhong
    Lu, Zhen-Hai
    Wang, Gao-Yuan
    Yue, Xin
    Huang, Wenlin
    Liu, Ran-Yi
    JOURNAL FOR IMMUNOTHERAPY OF CANCER, 2021, 9 (02)
  • [42] Prognostic impact of neutrophils-to-lymphocytes ratio (NLR), PD-L1 expression, and tumor immune microenvironment in laryngeal cancer
    Franz, Leonardo
    Alessandrini, Lara
    Fasanaro, Elena
    Gaudioso, Piergiorgio
    Carli, Alessandro
    Nicolai, Piero
    Marioni, Gino
    ANNALS OF DIAGNOSTIC PATHOLOGY, 2021, 50
  • [43] Paper m6A methyltransferase METTL16 mediates immune evasion of colorectal cancer cells via epigenetically regulating PD-L1 expression
    Wang, Ailei
    Sun, Yingjie
    Wang, Xince
    Yan, Zhaofei
    Wang, Dongsheng
    Zeng, Li
    Lu, Qingge
    AGING-US, 2023, 15 (16): : 8444 - 8457
  • [44] Immune checkpoint molecules B7-H6 and PD-L1 co-pattern the tumor inflammatory microenvironment in human breast cancer
    Cherif, Boutheina
    Triki, Hana
    Charfi, Slim
    Bouzidi, Lobna
    Kridis, Wala Ben
    Khanfir, Afef
    Chaabane, Kais
    Sellami-Boudawara, Tahya
    Rebai, Ahmed
    SCIENTIFIC REPORTS, 2021, 11 (01)
  • [45] RNA methylation-related genes of m6A, m5C, and m1A predict prognosis and immunotherapy response in cervical cancer
    Wang, Yan
    Mao, Yiwen
    Wang, Caizhi
    Jiang, Xuefeng
    Tang, Qionglan
    Wang, Lingling
    Zhu, Jialei
    Zhao, Mengqiu
    ANNALS OF MEDICINE, 2023, 55 (01)
  • [46] PD-L1 Expression in High-Risk Early-Stage Colorectal Cancer-Its Clinical and Biological Significance in Immune Microenvironment
    Chung, Bing-Syuan
    Liao, I-Chuang
    Lin, Peng-Chan
    Wu, Shang-Yin
    Kang, Jui-Wen
    Lin, Bo-Wen
    Chen, Po-Chuan
    Chan, Ren-Hao
    Lee, Chung-Ta
    Shen, Meng-Ru
    Chen, Shang-Hung
    Yeh, Yu-Min
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2022, 23 (21)
  • [47] Overexpression of CD155 is associated with PD-1 and PD-L1 expression on immune cells, rather than tumor cells in the breast cancer microenvironment
    Wang, Rui-Bin
    Li, Yu-Chen
    Zhou, Quan
    Lv, Shu-Zhen
    Yuan, Ke-Yu
    Wu, Jiang-Ping
    Zhao, Yan-Jie
    Song, Qing-Kun
    Zhu, Bin
    WORLD JOURNAL OF CLINICAL CASES, 2020, 8 (23) : 5935 - 5943
  • [48] Tumor-Associated CD 163+ M2 Macrophage Infiltration is Highly Associated with PD-L1 Expression in Cervical Cancer
    Guo, Fan
    Feng, Yang-chun
    Zhao, Gang
    Zhang, Ran
    Cheng, Zhen-zhen
    Kong, Wei-na
    Wu, Hui-li
    Xu, Bin
    Lv, Xiang
    Ma, Xiu-min
    CANCER MANAGEMENT AND RESEARCH, 2020, 12 : 5831 - 5843
  • [49] Spatially Resolved Whole-Transcriptomic and Proteomic Profiling of Lung Cancer and Its Immune Microenvironment According to PD-L1 Expression
    Koh, Jaemoon
    Lee, Dongjoo
    Kim, Sehui
    Song, Seung Geun
    Han, Bogyeong
    Jeong, Hyein
    Kim, Young A.
    Keam, Bhumsuk
    Lee, Se-Hoon
    Kim, Kwangsoo
    Jeon, Yoon Kyung
    Chung, Doo Hyun
    CANCER IMMUNOLOGY RESEARCH, 2024, 12 (12) : 1753 - 1764
  • [50] Integrin-Linked Kinase Expression Characterizes the Immunosuppressive Tumor Microenvironment in Colorectal Cancer and Regulates PD-L1 Expression and Immune Cell Cytotoxicity
    Almasabi, Saleh
    Boyd, Richard
    Ahmed, Afsar U.
    Williams, Bryan R. G.
    FRONTIERS IN ONCOLOGY, 2022, 12