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

Multiple myeloma (MM) is a hematological malignancy in which plasma cells proliferate abnormally. 5-methylcytosine (mC) 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 mC modifications and how the immune microenvironment is linked to mC methylation in MM. A total of 483 samples (60 healthy samples, 423 MM samples) from the Gene Expression Omnibus dataset were acquired to assess the expression of mC regulators. A nomogram model was established to predict the occurrence of MM. We investigated the impact of mC modification on immune microenvironment characteristics, such as the infiltration of immunocytes and immune response reactions. We then systematically evaluated three different mC expression patterns to assess immune characteristics and metabolic functional pathways and established mC-related differentially expressed genes (DEGs). In addition, biological process analysis was performed and an mC score was constructed to identify potentially significant immunological functions in MM. Differential expressions of mC regulators were identified between healthy and MM samples. The nomogram revealed that mC regulators could predict higher disease occurrence of MM. We identified three distinct mC clusters with unique immunological and metabolic characteristics. Among the three different mC clusters, cluster C had more immune characteristics and more metabolism-related pathways than clusters A and B. We analyzed 256 mC-related DEGs and classified the samples into three different mC gene clusters. Based on the mC and mC gene clusters, we calculated mC scores and classified each patient into high- and low-mC score groups. Our study demonstrated that mC 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.