Abstract
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.