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m5C Regulator-mediated methylation modification clusters contribute to the immune microenvironment regulation of multiple myeloma

Authors :
Hefei Ren
Chang Liu
Hongkun Wu
Zhenhua Wang
Sai Chen
Xiaomin Zhang
Jigang Ren
Huiying Qiu
Lin Zhou
Source :
Frontiers in Genetics, Vol 13 (2022)
Publication Year :
2022
Publisher :
Frontiers Media S.A., 2022.

Abstract

Background: Multiple myeloma (MM) is a hematological malignancy in which plasma cells proliferate abnormally. 5-methylcytosine (m5C) 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 m5C modifications and how the immune microenvironment is linked to m5C 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 m5C regulators. A nomogram model was established to predict the occurrence of MM. We investigated the impact of m5C modification on immune microenvironment characteristics, such as the infiltration of immunocytes and immune response reactions. We then systematically evaluated three different m5C expression patterns to assess immune characteristics and metabolic functional pathways and established m5C-related differentially expressed genes (DEGs). In addition, biological process analysis was performed and an m5C score was constructed to identify potentially significant immunological functions in MM.Result: Differential expressions of m5C regulators were identified between healthy and MM samples. The nomogram revealed that m5C regulators could predict higher disease occurrence of MM. We identified three distinct m5C clusters with unique immunological and metabolic characteristics. Among the three different m5C clusters, cluster C had more immune characteristics and more metabolism-related pathways than clusters A and B. We analyzed 256 m5C-related DEGs and classified the samples into three different m5C gene clusters. Based on the m5C and m5C gene clusters, we calculated m5C scores and classified each patient into high- and low-m5C score groups.Conclusion: Our study demonstrated that m5C 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.

Details

Language :
English
ISSN :
16648021
Volume :
13
Database :
Directory of Open Access Journals
Journal :
Frontiers in Genetics
Publication Type :
Academic Journal
Accession number :
edsdoj.8f9595c44a4ef78335c9a71e063853
Document Type :
article
Full Text :
https://doi.org/10.3389/fgene.2022.920164