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

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...

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Autores principales: Ji, Huihui, Zhang, Jian-an, Liu, Hejing, Li, Kehan, Wang, Zhi-wei, Zhu, Xueqiong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9458859/
https://www.ncbi.nlm.nih.gov/pubmed/36091006
http://dx.doi.org/10.3389/fimmu.2022.976107
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author Ji, Huihui
Zhang, Jian-an
Liu, Hejing
Li, Kehan
Wang, Zhi-wei
Zhu, Xueqiong
author_facet Ji, Huihui
Zhang, Jian-an
Liu, Hejing
Li, Kehan
Wang, Zhi-wei
Zhu, Xueqiong
author_sort Ji, Huihui
collection PubMed
description 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.
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spelling pubmed-94588592022-09-10 Comprehensive characterization of tumor microenvironment and m6A RNA methylation regulators and its effects on PD-L1 and immune infiltrates in cervical cancer Ji, Huihui Zhang, Jian-an Liu, Hejing Li, Kehan Wang, Zhi-wei Zhu, Xueqiong Front Immunol Immunology 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. Frontiers Media S.A. 2022-08-26 /pmc/articles/PMC9458859/ /pubmed/36091006 http://dx.doi.org/10.3389/fimmu.2022.976107 Text en Copyright © 2022 Ji, Zhang, Liu, Li, Wang and Zhu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Ji, Huihui
Zhang, Jian-an
Liu, Hejing
Li, Kehan
Wang, Zhi-wei
Zhu, Xueqiong
Comprehensive characterization of tumor microenvironment and m6A RNA methylation regulators and its effects on PD-L1 and immune infiltrates in cervical cancer
title Comprehensive characterization of tumor microenvironment and m6A RNA methylation regulators and its effects on PD-L1 and immune infiltrates in cervical cancer
title_full Comprehensive characterization of tumor microenvironment and m6A RNA methylation regulators and its effects on PD-L1 and immune infiltrates in cervical cancer
title_fullStr Comprehensive characterization of tumor microenvironment and m6A RNA methylation regulators and its effects on PD-L1 and immune infiltrates in cervical cancer
title_full_unstemmed Comprehensive characterization of tumor microenvironment and m6A RNA methylation regulators and its effects on PD-L1 and immune infiltrates in cervical cancer
title_short Comprehensive characterization of tumor microenvironment and m6A RNA methylation regulators and its effects on PD-L1 and immune infiltrates in cervical cancer
title_sort comprehensive characterization of tumor microenvironment and m6a rna methylation regulators and its effects on pd-l1 and immune infiltrates in cervical cancer
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9458859/
https://www.ncbi.nlm.nih.gov/pubmed/36091006
http://dx.doi.org/10.3389/fimmu.2022.976107
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