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m5C regulator-mediated methylation modification phenotypes characterized by distinct tumor microenvironment immune heterogenicity in colorectal cancer

The RNA 5-methylcytosine (m5C) modification has been demonstrated to be an important epigenetic regulator and to impact colorectal cancer (CRC) progression. However, the potential roles of m5C modification in immune cell infiltration in the CRC tumor microenvironment (TME) remain unknown. The m5C mo...

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Autores principales: Chen, Zhihua, Li, Quanfa, Lin, Yilin, Lin, Suyong, Gao, Ji, Chen, Shaoqin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10366215/
https://www.ncbi.nlm.nih.gov/pubmed/37488178
http://dx.doi.org/10.1038/s41598-023-37300-z
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author Chen, Zhihua
Li, Quanfa
Lin, Yilin
Lin, Suyong
Gao, Ji
Chen, Shaoqin
author_facet Chen, Zhihua
Li, Quanfa
Lin, Yilin
Lin, Suyong
Gao, Ji
Chen, Shaoqin
author_sort Chen, Zhihua
collection PubMed
description The RNA 5-methylcytosine (m5C) modification has been demonstrated to be an important epigenetic regulator and to impact colorectal cancer (CRC) progression. However, the potential roles of m5C modification in immune cell infiltration in the CRC tumor microenvironment (TME) remain unknown. The m5C modification phenotypes were comprehensively evaluated based on 14 m5C regulators in a meta-CRC cohort of 1792 patients and systematically correlated with the m5C modification phenotypes, immune cell infiltration characteristics and known biological processes. The m5Cscore model was constructed by principal component analysis (PCA) algorithms to quantify the m5C modification phenotypes of individual CRC samples and was used to predict the immunotherapy response. We identified three m5C modification phenotypes associated with distinct clinical outcomes and biological processes among the 1792 meta-CRC patients. Three phenotypes with a highly consistent TME landscape and characteristics were revealed: immune excluded, immune desert and immune inflammation. The meta-CRC patients were divided into high and low m5Cscore subgroups based on the m5Cscore. The m5Cscore was confirmed to have a negative correlation with infiltrating immune cells and PD-L1 expression and a positive correlation with tumor mutation burden (TMB), mutation rate and microsatellite instability (MSI) score. Moreover, patients in the low m5Cscore group had better immunotherapy responses and significant durable survival benefits in independent anti-PD-1/L1 immunotherapy cohorts for the immune checkpoint inhibitor (ICI) therapeutic strategy. This study revealed that m5C modification plays a crucial role in TME composition and complexity. Comprehensive evaluation of the m5C modification phenotypes of individual patients will enhance our understanding of TME characteristics and promote the application of more appropriate and personalized treatment strategies.
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spelling pubmed-103662152023-07-26 m5C regulator-mediated methylation modification phenotypes characterized by distinct tumor microenvironment immune heterogenicity in colorectal cancer Chen, Zhihua Li, Quanfa Lin, Yilin Lin, Suyong Gao, Ji Chen, Shaoqin Sci Rep Article The RNA 5-methylcytosine (m5C) modification has been demonstrated to be an important epigenetic regulator and to impact colorectal cancer (CRC) progression. However, the potential roles of m5C modification in immune cell infiltration in the CRC tumor microenvironment (TME) remain unknown. The m5C modification phenotypes were comprehensively evaluated based on 14 m5C regulators in a meta-CRC cohort of 1792 patients and systematically correlated with the m5C modification phenotypes, immune cell infiltration characteristics and known biological processes. The m5Cscore model was constructed by principal component analysis (PCA) algorithms to quantify the m5C modification phenotypes of individual CRC samples and was used to predict the immunotherapy response. We identified three m5C modification phenotypes associated with distinct clinical outcomes and biological processes among the 1792 meta-CRC patients. Three phenotypes with a highly consistent TME landscape and characteristics were revealed: immune excluded, immune desert and immune inflammation. The meta-CRC patients were divided into high and low m5Cscore subgroups based on the m5Cscore. The m5Cscore was confirmed to have a negative correlation with infiltrating immune cells and PD-L1 expression and a positive correlation with tumor mutation burden (TMB), mutation rate and microsatellite instability (MSI) score. Moreover, patients in the low m5Cscore group had better immunotherapy responses and significant durable survival benefits in independent anti-PD-1/L1 immunotherapy cohorts for the immune checkpoint inhibitor (ICI) therapeutic strategy. This study revealed that m5C modification plays a crucial role in TME composition and complexity. Comprehensive evaluation of the m5C modification phenotypes of individual patients will enhance our understanding of TME characteristics and promote the application of more appropriate and personalized treatment strategies. Nature Publishing Group UK 2023-07-24 /pmc/articles/PMC10366215/ /pubmed/37488178 http://dx.doi.org/10.1038/s41598-023-37300-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Chen, Zhihua
Li, Quanfa
Lin, Yilin
Lin, Suyong
Gao, Ji
Chen, Shaoqin
m5C regulator-mediated methylation modification phenotypes characterized by distinct tumor microenvironment immune heterogenicity in colorectal cancer
title m5C regulator-mediated methylation modification phenotypes characterized by distinct tumor microenvironment immune heterogenicity in colorectal cancer
title_full m5C regulator-mediated methylation modification phenotypes characterized by distinct tumor microenvironment immune heterogenicity in colorectal cancer
title_fullStr m5C regulator-mediated methylation modification phenotypes characterized by distinct tumor microenvironment immune heterogenicity in colorectal cancer
title_full_unstemmed m5C regulator-mediated methylation modification phenotypes characterized by distinct tumor microenvironment immune heterogenicity in colorectal cancer
title_short m5C regulator-mediated methylation modification phenotypes characterized by distinct tumor microenvironment immune heterogenicity in colorectal cancer
title_sort m5c regulator-mediated methylation modification phenotypes characterized by distinct tumor microenvironment immune heterogenicity in colorectal cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10366215/
https://www.ncbi.nlm.nih.gov/pubmed/37488178
http://dx.doi.org/10.1038/s41598-023-37300-z
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