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m(5)C Regulator-mediated methylation modification clusters contribute to the immune microenvironment regulation of multiple myeloma

Background: Multiple myeloma (MM) is a hematological malignancy in which plasma cells proliferate abnormally. 5-methylcytosine (m(5)C) methylation modification is the primary epigenetic modification and is involved in regulating the occurrence, development, invasion, and metastasis of various tumors...

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Autores principales: Ren, Hefei, Liu, Chang, Wu, Hongkun, Wang, Zhenhua, Chen, Sai, Zhang, Xiaomin, Ren, Jigang, Qiu, Huiying, Zhou, Lin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9453209/
https://www.ncbi.nlm.nih.gov/pubmed/36092897
http://dx.doi.org/10.3389/fgene.2022.920164
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author Ren, Hefei
Liu, Chang
Wu, Hongkun
Wang, Zhenhua
Chen, Sai
Zhang, Xiaomin
Ren, Jigang
Qiu, Huiying
Zhou, Lin
author_facet Ren, Hefei
Liu, Chang
Wu, Hongkun
Wang, Zhenhua
Chen, Sai
Zhang, Xiaomin
Ren, Jigang
Qiu, Huiying
Zhou, Lin
author_sort Ren, Hefei
collection PubMed
description Background: Multiple myeloma (MM) is a hematological malignancy in which plasma cells proliferate abnormally. 5-methylcytosine (m(5)C) methylation modification is the primary epigenetic modification and is involved in regulating the occurrence, development, invasion, and metastasis of various tumors; however, its immunological functions have not been systematically described in MM. Thus, this study aimed to clarify the significance of m(5)C modifications and how the immune microenvironment is linked to m(5)C methylation in MM. Method: A total of 483 samples (60 healthy samples, 423 MM samples) from the Gene Expression Omnibus dataset were acquired to assess the expression of m(5)C regulators. A nomogram model was established to predict the occurrence of MM. We investigated the impact of m(5)C modification on immune microenvironment characteristics, such as the infiltration of immunocytes and immune response reactions. We then systematically evaluated three different m(5)C expression patterns to assess immune characteristics and metabolic functional pathways and established m(5)C-related differentially expressed genes (DEGs). In addition, biological process analysis was performed and an m(5)C score was constructed to identify potentially significant immunological functions in MM. Result: Differential expressions of m(5)C regulators were identified between healthy and MM samples. The nomogram revealed that m(5)C regulators could predict higher disease occurrence of MM. We identified three distinct m(5)C clusters with unique immunological and metabolic characteristics. Among the three different m(5)C clusters, cluster C had more immune characteristics and more metabolism-related pathways than clusters A and B. We analyzed 256 m(5)C-related DEGs and classified the samples into three different m(5)C gene clusters. Based on the m(5)C and m(5)C gene clusters, we calculated m(5)C scores and classified each patient into high- and low-m(5)C score groups. Conclusion: Our study demonstrated that m(5)C modification is involved in and contributes to the diversity and complexity of the immune microenvironment, which offers promise for the development of accurate therapeutic strategies.
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spelling pubmed-94532092022-09-09 m(5)C Regulator-mediated methylation modification clusters contribute to the immune microenvironment regulation of multiple myeloma Ren, Hefei Liu, Chang Wu, Hongkun Wang, Zhenhua Chen, Sai Zhang, Xiaomin Ren, Jigang Qiu, Huiying Zhou, Lin Front Genet Genetics Background: Multiple myeloma (MM) is a hematological malignancy in which plasma cells proliferate abnormally. 5-methylcytosine (m(5)C) methylation modification is the primary epigenetic modification and is involved in regulating the occurrence, development, invasion, and metastasis of various tumors; however, its immunological functions have not been systematically described in MM. Thus, this study aimed to clarify the significance of m(5)C modifications and how the immune microenvironment is linked to m(5)C methylation in MM. Method: A total of 483 samples (60 healthy samples, 423 MM samples) from the Gene Expression Omnibus dataset were acquired to assess the expression of m(5)C regulators. A nomogram model was established to predict the occurrence of MM. We investigated the impact of m(5)C modification on immune microenvironment characteristics, such as the infiltration of immunocytes and immune response reactions. We then systematically evaluated three different m(5)C expression patterns to assess immune characteristics and metabolic functional pathways and established m(5)C-related differentially expressed genes (DEGs). In addition, biological process analysis was performed and an m(5)C score was constructed to identify potentially significant immunological functions in MM. Result: Differential expressions of m(5)C regulators were identified between healthy and MM samples. The nomogram revealed that m(5)C regulators could predict higher disease occurrence of MM. We identified three distinct m(5)C clusters with unique immunological and metabolic characteristics. Among the three different m(5)C clusters, cluster C had more immune characteristics and more metabolism-related pathways than clusters A and B. We analyzed 256 m(5)C-related DEGs and classified the samples into three different m(5)C gene clusters. Based on the m(5)C and m(5)C gene clusters, we calculated m(5)C scores and classified each patient into high- and low-m(5)C score groups. Conclusion: Our study demonstrated that m(5)C modification is involved in and contributes to the diversity and complexity of the immune microenvironment, which offers promise for the development of accurate therapeutic strategies. Frontiers Media S.A. 2022-08-25 /pmc/articles/PMC9453209/ /pubmed/36092897 http://dx.doi.org/10.3389/fgene.2022.920164 Text en Copyright © 2022 Ren, Liu, Wu, Wang, Chen, Zhang, Ren, Qiu and Zhou. 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 Genetics
Ren, Hefei
Liu, Chang
Wu, Hongkun
Wang, Zhenhua
Chen, Sai
Zhang, Xiaomin
Ren, Jigang
Qiu, Huiying
Zhou, Lin
m(5)C Regulator-mediated methylation modification clusters contribute to the immune microenvironment regulation of multiple myeloma
title m(5)C Regulator-mediated methylation modification clusters contribute to the immune microenvironment regulation of multiple myeloma
title_full m(5)C Regulator-mediated methylation modification clusters contribute to the immune microenvironment regulation of multiple myeloma
title_fullStr m(5)C Regulator-mediated methylation modification clusters contribute to the immune microenvironment regulation of multiple myeloma
title_full_unstemmed m(5)C Regulator-mediated methylation modification clusters contribute to the immune microenvironment regulation of multiple myeloma
title_short m(5)C Regulator-mediated methylation modification clusters contribute to the immune microenvironment regulation of multiple myeloma
title_sort m(5)c regulator-mediated methylation modification clusters contribute to the immune microenvironment regulation of multiple myeloma
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9453209/
https://www.ncbi.nlm.nih.gov/pubmed/36092897
http://dx.doi.org/10.3389/fgene.2022.920164
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