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m5C regulator-mediated modification patterns and tumor microenvironment infiltration characterization in colorectal cancer: One step closer to precision medicine

BACKGROUND: The RNA modification 5-methylcytosine (m5C) is one of the most prevalent post-transcriptional modifications, with increasing evidence demonstrating its extensive involvement in the tumorigenesis and progression of various cancers. Colorectal cancer (CRC) is the third most common cancer a...

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Autores principales: Chen, Baoxiang, Xi, Yiqing, Zhao, Jianhong, Hong, Yuntian, Tian, Shunhua, Zhai, Xiang, Chen, Quanjiao, Ren, Xianghai, Fan, Lifang, Xie, Xiaoyu, Jiang, Congqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9751490/
https://www.ncbi.nlm.nih.gov/pubmed/36532062
http://dx.doi.org/10.3389/fimmu.2022.1049435
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author Chen, Baoxiang
Xi, Yiqing
Zhao, Jianhong
Hong, Yuntian
Tian, Shunhua
Zhai, Xiang
Chen, Quanjiao
Ren, Xianghai
Fan, Lifang
Xie, Xiaoyu
Jiang, Congqing
author_facet Chen, Baoxiang
Xi, Yiqing
Zhao, Jianhong
Hong, Yuntian
Tian, Shunhua
Zhai, Xiang
Chen, Quanjiao
Ren, Xianghai
Fan, Lifang
Xie, Xiaoyu
Jiang, Congqing
author_sort Chen, Baoxiang
collection PubMed
description BACKGROUND: The RNA modification 5-methylcytosine (m5C) is one of the most prevalent post-transcriptional modifications, with increasing evidence demonstrating its extensive involvement in the tumorigenesis and progression of various cancers. Colorectal cancer (CRC) is the third most common cancer and second leading cause of cancer-related deaths worldwide. However, the role of m5C modulators in shaping tumor microenvironment (TME) heterogeneity and regulating immune cell infiltration in CRC requires further clarification. RESULTS: The transcriptomic sequencing data of 18 m5C regulators and clinical data of patients with CRC were obtained from The Cancer Genome Atlas (TCGA) and systematically evaluated. We found that 16 m5C regulators were differentially expressed between CRC and normal tissues. Unsupervised cluster analysis was then performed and revealed two distinct m5C modification patterns that yielded different clinical prognoses and biological functions in CRC. We demonstrated that the m5C score constructed from eight m5C-related genes showed excellent prognostic performance, with a subsequent independent analysis confirming its predictive ability in the CRC cohort. Then we developed a nomogram containing five clinical risk factors and the m5C risk score and found that the m5C score exhibited high prognostic prediction accuracy and favorable clinical applicability. Moreover, the CRC patients with low m5C score were characterized by “hot” TME exhibiting increased immune cell infiltration and higher immune checkpoint expression. These characteristics were highlighted as potential identifiers of suitable candidates for anticancer immunotherapy. Although the high m5C score represented the non-inflammatory phenotype, the CRC patients in this group exhibited high level of sensitivity to molecular-targeted therapy. CONCLUSION: Our comprehensive analysis indicated that the novel m5C clusters and scoring system accurately reflected the distinct prognostic signature, clinicopathological characteristics, immunological phenotypes, and stratifying therapeutic opportunities of CRC. Our findings, therefore, offer valuable insights into factors that may be targeted in the development of precision medicine-based therapeutic strategies for CRC.
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spelling pubmed-97514902022-12-16 m5C regulator-mediated modification patterns and tumor microenvironment infiltration characterization in colorectal cancer: One step closer to precision medicine Chen, Baoxiang Xi, Yiqing Zhao, Jianhong Hong, Yuntian Tian, Shunhua Zhai, Xiang Chen, Quanjiao Ren, Xianghai Fan, Lifang Xie, Xiaoyu Jiang, Congqing Front Immunol Immunology BACKGROUND: The RNA modification 5-methylcytosine (m5C) is one of the most prevalent post-transcriptional modifications, with increasing evidence demonstrating its extensive involvement in the tumorigenesis and progression of various cancers. Colorectal cancer (CRC) is the third most common cancer and second leading cause of cancer-related deaths worldwide. However, the role of m5C modulators in shaping tumor microenvironment (TME) heterogeneity and regulating immune cell infiltration in CRC requires further clarification. RESULTS: The transcriptomic sequencing data of 18 m5C regulators and clinical data of patients with CRC were obtained from The Cancer Genome Atlas (TCGA) and systematically evaluated. We found that 16 m5C regulators were differentially expressed between CRC and normal tissues. Unsupervised cluster analysis was then performed and revealed two distinct m5C modification patterns that yielded different clinical prognoses and biological functions in CRC. We demonstrated that the m5C score constructed from eight m5C-related genes showed excellent prognostic performance, with a subsequent independent analysis confirming its predictive ability in the CRC cohort. Then we developed a nomogram containing five clinical risk factors and the m5C risk score and found that the m5C score exhibited high prognostic prediction accuracy and favorable clinical applicability. Moreover, the CRC patients with low m5C score were characterized by “hot” TME exhibiting increased immune cell infiltration and higher immune checkpoint expression. These characteristics were highlighted as potential identifiers of suitable candidates for anticancer immunotherapy. Although the high m5C score represented the non-inflammatory phenotype, the CRC patients in this group exhibited high level of sensitivity to molecular-targeted therapy. CONCLUSION: Our comprehensive analysis indicated that the novel m5C clusters and scoring system accurately reflected the distinct prognostic signature, clinicopathological characteristics, immunological phenotypes, and stratifying therapeutic opportunities of CRC. Our findings, therefore, offer valuable insights into factors that may be targeted in the development of precision medicine-based therapeutic strategies for CRC. Frontiers Media S.A. 2022-12-01 /pmc/articles/PMC9751490/ /pubmed/36532062 http://dx.doi.org/10.3389/fimmu.2022.1049435 Text en Copyright © 2022 Chen, Xi, Zhao, Hong, Tian, Zhai, Chen, Ren, Fan, Xie and Jiang 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
Chen, Baoxiang
Xi, Yiqing
Zhao, Jianhong
Hong, Yuntian
Tian, Shunhua
Zhai, Xiang
Chen, Quanjiao
Ren, Xianghai
Fan, Lifang
Xie, Xiaoyu
Jiang, Congqing
m5C regulator-mediated modification patterns and tumor microenvironment infiltration characterization in colorectal cancer: One step closer to precision medicine
title m5C regulator-mediated modification patterns and tumor microenvironment infiltration characterization in colorectal cancer: One step closer to precision medicine
title_full m5C regulator-mediated modification patterns and tumor microenvironment infiltration characterization in colorectal cancer: One step closer to precision medicine
title_fullStr m5C regulator-mediated modification patterns and tumor microenvironment infiltration characterization in colorectal cancer: One step closer to precision medicine
title_full_unstemmed m5C regulator-mediated modification patterns and tumor microenvironment infiltration characterization in colorectal cancer: One step closer to precision medicine
title_short m5C regulator-mediated modification patterns and tumor microenvironment infiltration characterization in colorectal cancer: One step closer to precision medicine
title_sort m5c regulator-mediated modification patterns and tumor microenvironment infiltration characterization in colorectal cancer: one step closer to precision medicine
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9751490/
https://www.ncbi.nlm.nih.gov/pubmed/36532062
http://dx.doi.org/10.3389/fimmu.2022.1049435
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