Microchromosome maintenance protein 2 is essential in immune infiltration-correlated prognosis of multiple myeloma patients by regulating cell cycle

PURPOSE: Multiple myeloma (MM) is a common hematological malignancy, while the prognostic value of tumor-infiltrating immune cells in MM remains elusive. This study aimed to construct an immune-related prognostic model and identify potential therapeutic targets for MM. METHODS: RNA-seq and clinical data of 751 newly diagnosed MM patients were analyzed. LASSO regression was applied to establish an immune pathway-based prognostic model for patient risk stratification. WGCNA was used to screen hub genes, and in vitro and in vivo experiments validated gene functions and therapeutic effects. RESULTS: Five immune cell pathways were significantly correlated with MM prognosis. MCM2 was identified as the key hub gene associated with risk scores. MCM2 knockdown induced G2-phase cell cycle arrest and suppressed MM proliferation both in vitro and in vivo. Moreover, MCM2 inhibition enhanced the antitumor efficacy of PD1/PDL1 inhibitor BMS1, and CDK inhibitor PHA767491 sensitized MM to immunotherapy. CONCLUSION: The immune-based model reliably predicts MM prognosis. MCM2 serves as a vital prognostic biomarker. Targeting MCM2 combined with PD1/PDL1 and CDK inhibitors represents a promising therapeutic strategy for MM.