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The significance of m6A RNA methylation modification in prognosis and tumor microenvironment immune infiltration of cervical cancer

Recent studies have highlighted that N6-methyladenosine (m6A) plays a significant role in tumorigenicity and progression. However, the mechanism of m6A modifications in the tumor microenvironment (TME) immune cell infiltration in cervical cancer (CC) remains unclear. Clinical and RNA sequencing data...

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Autores principales: Guo, Yilin, Bai, Yangyang, Wang, Lu, Xu, Zhen, Wang, Xiliang, Wang, Wuliang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9239609/
https://www.ncbi.nlm.nih.gov/pubmed/35777046
http://dx.doi.org/10.1097/MD.0000000000029818
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author Guo, Yilin
Bai, Yangyang
Wang, Lu
Xu, Zhen
Wang, Xiliang
Wang, Wuliang
author_facet Guo, Yilin
Bai, Yangyang
Wang, Lu
Xu, Zhen
Wang, Xiliang
Wang, Wuliang
author_sort Guo, Yilin
collection PubMed
description Recent studies have highlighted that N6-methyladenosine (m6A) plays a significant role in tumorigenicity and progression. However, the mechanism of m6A modifications in the tumor microenvironment (TME) immune cell infiltration in cervical cancer (CC) remains unclear. Clinical and RNA sequencing data of 25 m6A RNA methylation regulators were acquired from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. LASSO Cox regression analysis was used to generate a prognostic risk signature. m6A modification patterns were identified based on the expression of 25 m6A regulators, and their correlation with TME immune cell-infiltrating characterization was analyzed. Principal component analysis was used to construct an m6A-scoring signature (m6A score) to evaluate the m6A modification patterns of individual CC samples and guide the selection of more effective immunotherapeutic strategies. Genetic and expression alterations of 25 m6A regulators were highly heterogeneous between CC and normal tissues. METTL14 and IGF2BP1 were selected to conduct the prognostic risk signature. Three m6A modification patterns were identified in 659 CC samples, which were associated with distinct clinical outcomes and biological pathways. The TME immune cell-infiltrating characterization of the three m6A modification patterns was highly consistent with 3 tumor immune phenotypes, including immune-excluded, immune-inflamed, and immune-desert phenotypes. Due to the heterogeneity of m6A modification patterns, an m6A scoring signature was established to evaluate the m6A modification patterns of individual CC samples. Univariate and multivariate Cox regression analyses revealed that the m6A score is a robust and independent prognostic biomarker for assessing the prognosis of CC patients. A low m6A score, characterized by higher somatic mutation and higher expression of proliferation-related and DNA repair-related genes, indicated poor overall survival. Activation of immune infiltration was exhibited by the high m6A score, which was likely to have a good response and clinical benefits to antiPD-1/L1 immunotherapy. This study highlights the prognostic value of 25 m6A regulators in CC. The m6A modification is related to immune regulation and the formation of TME heterogeneity and complexity. An m6A scoring signature to clarify the individual m6A modification pattern could enhance our understanding of TME immune cell-infiltrating characterization and guide immunotherapy strategies.
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spelling pubmed-92396092022-06-30 The significance of m6A RNA methylation modification in prognosis and tumor microenvironment immune infiltration of cervical cancer Guo, Yilin Bai, Yangyang Wang, Lu Xu, Zhen Wang, Xiliang Wang, Wuliang Medicine (Baltimore) Research Article Recent studies have highlighted that N6-methyladenosine (m6A) plays a significant role in tumorigenicity and progression. However, the mechanism of m6A modifications in the tumor microenvironment (TME) immune cell infiltration in cervical cancer (CC) remains unclear. Clinical and RNA sequencing data of 25 m6A RNA methylation regulators were acquired from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. LASSO Cox regression analysis was used to generate a prognostic risk signature. m6A modification patterns were identified based on the expression of 25 m6A regulators, and their correlation with TME immune cell-infiltrating characterization was analyzed. Principal component analysis was used to construct an m6A-scoring signature (m6A score) to evaluate the m6A modification patterns of individual CC samples and guide the selection of more effective immunotherapeutic strategies. Genetic and expression alterations of 25 m6A regulators were highly heterogeneous between CC and normal tissues. METTL14 and IGF2BP1 were selected to conduct the prognostic risk signature. Three m6A modification patterns were identified in 659 CC samples, which were associated with distinct clinical outcomes and biological pathways. The TME immune cell-infiltrating characterization of the three m6A modification patterns was highly consistent with 3 tumor immune phenotypes, including immune-excluded, immune-inflamed, and immune-desert phenotypes. Due to the heterogeneity of m6A modification patterns, an m6A scoring signature was established to evaluate the m6A modification patterns of individual CC samples. Univariate and multivariate Cox regression analyses revealed that the m6A score is a robust and independent prognostic biomarker for assessing the prognosis of CC patients. A low m6A score, characterized by higher somatic mutation and higher expression of proliferation-related and DNA repair-related genes, indicated poor overall survival. Activation of immune infiltration was exhibited by the high m6A score, which was likely to have a good response and clinical benefits to antiPD-1/L1 immunotherapy. This study highlights the prognostic value of 25 m6A regulators in CC. The m6A modification is related to immune regulation and the formation of TME heterogeneity and complexity. An m6A scoring signature to clarify the individual m6A modification pattern could enhance our understanding of TME immune cell-infiltrating characterization and guide immunotherapy strategies. Lippincott Williams & Wilkins 2022-06-30 /pmc/articles/PMC9239609/ /pubmed/35777046 http://dx.doi.org/10.1097/MD.0000000000029818 Text en Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY) (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Guo, Yilin
Bai, Yangyang
Wang, Lu
Xu, Zhen
Wang, Xiliang
Wang, Wuliang
The significance of m6A RNA methylation modification in prognosis and tumor microenvironment immune infiltration of cervical cancer
title The significance of m6A RNA methylation modification in prognosis and tumor microenvironment immune infiltration of cervical cancer
title_full The significance of m6A RNA methylation modification in prognosis and tumor microenvironment immune infiltration of cervical cancer
title_fullStr The significance of m6A RNA methylation modification in prognosis and tumor microenvironment immune infiltration of cervical cancer
title_full_unstemmed The significance of m6A RNA methylation modification in prognosis and tumor microenvironment immune infiltration of cervical cancer
title_short The significance of m6A RNA methylation modification in prognosis and tumor microenvironment immune infiltration of cervical cancer
title_sort significance of m6a rna methylation modification in prognosis and tumor microenvironment immune infiltration of cervical cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9239609/
https://www.ncbi.nlm.nih.gov/pubmed/35777046
http://dx.doi.org/10.1097/MD.0000000000029818
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