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.