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Molecular features, biological behaviors and clinical implications of m(5)C RNA methylation modification regulators in gastrointestinal cancers
Epitranscriptome studies have shown that critical RNA modifications drive tumorigenicity; however, the role of 5-methylcytosine (m(5)C) RNA methylation remains poorly understood. We extracted 17 m(5)C regulators and clustered distinct m(5)C modification patterns by consensus clustering analysis. Gen...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10281471/ https://www.ncbi.nlm.nih.gov/pubmed/37332118 http://dx.doi.org/10.1080/15384047.2023.2223382 |
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author | Zhan, Mengyao Song, Huan Tian, Dan Wen, Qin Shi, Xinling Wang, Yuting Mao, Xuhua Wang, Jianming |
author_facet | Zhan, Mengyao Song, Huan Tian, Dan Wen, Qin Shi, Xinling Wang, Yuting Mao, Xuhua Wang, Jianming |
author_sort | Zhan, Mengyao |
collection | PubMed |
description | Epitranscriptome studies have shown that critical RNA modifications drive tumorigenicity; however, the role of 5-methylcytosine (m(5)C) RNA methylation remains poorly understood. We extracted 17 m(5)C regulators and clustered distinct m(5)C modification patterns by consensus clustering analysis. Gene set variation and single-sample gene set enrichment analysis were applied to quantify functional analysis and immune infiltration. The least absolute shrinkage and selection operator was employed to develop a prognostic risk score. Kaplan-Meier with log-rank test was used for survival analysis. Differential expression analysis was performed with the “limma” R package. Wilcoxon signed ranked test or Kruskal-Wallis test was used to compare groups. We observed that m(5)C RNA methylation was commonly upregulated in gastrointestinal cancer and related to prognosis. Clusters were identified for m(5)C patterns, with distinct immune infiltrations and functional pathways. The risk scores of m(5)C regulators were independent risk factors. Differentially expressed mRNAs (DEmRNAs) in m(5)C clusters were involved in cancer-related pathways. The methylation-based m(5)Cscore showed a significant effect on the prognosis. Patients with a lower m(5)Cscore exhibited more therapeutic efficiency on anti-CTLA4 therapy in liver cancer, while the combination of anti-CTLA4 therapy and pd1 was more efficient for patients with a lower m(5)Cscore in pancreatic cancer. We uncovered dysregulations of m(5)C-related regulators in gastrointestinal cancer and their associations with overall survival. Some immune cells were differently infiltrated in distinct m(5)C modification patterns, indicating their potential impacts on gastrointestinal cancer cell-immune. Moreover, an m(5)Cscore, derived from DEmRNAs in specific clusters, can serve as a classifier for immunotherapy. |
format | Online Article Text |
id | pubmed-10281471 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-102814712023-06-21 Molecular features, biological behaviors and clinical implications of m(5)C RNA methylation modification regulators in gastrointestinal cancers Zhan, Mengyao Song, Huan Tian, Dan Wen, Qin Shi, Xinling Wang, Yuting Mao, Xuhua Wang, Jianming Cancer Biol Ther Research Paper Epitranscriptome studies have shown that critical RNA modifications drive tumorigenicity; however, the role of 5-methylcytosine (m(5)C) RNA methylation remains poorly understood. We extracted 17 m(5)C regulators and clustered distinct m(5)C modification patterns by consensus clustering analysis. Gene set variation and single-sample gene set enrichment analysis were applied to quantify functional analysis and immune infiltration. The least absolute shrinkage and selection operator was employed to develop a prognostic risk score. Kaplan-Meier with log-rank test was used for survival analysis. Differential expression analysis was performed with the “limma” R package. Wilcoxon signed ranked test or Kruskal-Wallis test was used to compare groups. We observed that m(5)C RNA methylation was commonly upregulated in gastrointestinal cancer and related to prognosis. Clusters were identified for m(5)C patterns, with distinct immune infiltrations and functional pathways. The risk scores of m(5)C regulators were independent risk factors. Differentially expressed mRNAs (DEmRNAs) in m(5)C clusters were involved in cancer-related pathways. The methylation-based m(5)Cscore showed a significant effect on the prognosis. Patients with a lower m(5)Cscore exhibited more therapeutic efficiency on anti-CTLA4 therapy in liver cancer, while the combination of anti-CTLA4 therapy and pd1 was more efficient for patients with a lower m(5)Cscore in pancreatic cancer. We uncovered dysregulations of m(5)C-related regulators in gastrointestinal cancer and their associations with overall survival. Some immune cells were differently infiltrated in distinct m(5)C modification patterns, indicating their potential impacts on gastrointestinal cancer cell-immune. Moreover, an m(5)Cscore, derived from DEmRNAs in specific clusters, can serve as a classifier for immunotherapy. Taylor & Francis 2023-06-18 /pmc/articles/PMC10281471/ /pubmed/37332118 http://dx.doi.org/10.1080/15384047.2023.2223382 Text en © 2023 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent. |
spellingShingle | Research Paper Zhan, Mengyao Song, Huan Tian, Dan Wen, Qin Shi, Xinling Wang, Yuting Mao, Xuhua Wang, Jianming Molecular features, biological behaviors and clinical implications of m(5)C RNA methylation modification regulators in gastrointestinal cancers |
title | Molecular features, biological behaviors and clinical implications of m(5)C RNA methylation modification regulators in gastrointestinal cancers |
title_full | Molecular features, biological behaviors and clinical implications of m(5)C RNA methylation modification regulators in gastrointestinal cancers |
title_fullStr | Molecular features, biological behaviors and clinical implications of m(5)C RNA methylation modification regulators in gastrointestinal cancers |
title_full_unstemmed | Molecular features, biological behaviors and clinical implications of m(5)C RNA methylation modification regulators in gastrointestinal cancers |
title_short | Molecular features, biological behaviors and clinical implications of m(5)C RNA methylation modification regulators in gastrointestinal cancers |
title_sort | molecular features, biological behaviors and clinical implications of m(5)c rna methylation modification regulators in gastrointestinal cancers |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10281471/ https://www.ncbi.nlm.nih.gov/pubmed/37332118 http://dx.doi.org/10.1080/15384047.2023.2223382 |
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