UAP1 as a prognostic biomarker regulating malignant biological functions in multiple myeloma cells.

BACKGROUND

Multiple myeloma (MM) is a hematological malignancy characterized by proliferation of malignant plasma cells. UDP-N-acetylglucosamine pyrophosphorylase 1 (UAP1) has been shown to promote progression in various cancers. However, its specific role in MM remains unclear.

METHODS

We analyzed six datasets comprising 3,117 patients from the Multiple Myeloma Research Foundation and Gene Expression Omnibus databases. The reliability of UAP1 as a prognostic predictor was also systematically evaluated. To further elucidate the specific mechanisms underlying the role of UAP1 in promoting MM progression, we performed an in-depth analysis of single-cell RNA sequencing data from 24 patients with MM. Additionally, we evaluated UAP1's therapeutic potential using two MM cell lines (RPMI-8226 and U266).

RESULTS

Across all 3,117 patients with MM, high UAP1 expression correlated with significantly worse overall survival, event-free survival, and progression-free survival. Patients with high UAP1 expression consistently exhibited concurrent genetic abnormalities. Single-cell data suggest that UAP1 is predominantly expressed in tumor cells, is closely associated with tumor cell differentiation signatures, and shows a correlative link with the expression of immunosuppressive pathway components. In vitro experiments demonstrated that UAP1 knockdown significantly inhibited cell proliferation and cell cycle progression, enhanced apoptosis, and increased the dexamethasone sensitivity of RPMI-8226 and U266 cells. Genetic knockdown of UAP1 significantly increased the proportion of CD8+ T cells in in vitro co-culture system with MM cells.

CONCLUSIONS

UAP1 expression is significantly correlated with tumor differentiation, proliferation, immunosuppression, and patient prognosis, establishing it as an prognostic biomarker Regulating Malignant Biological Functions in Multiple Myeloma Cells. Our findings may guide the development of novel treatment strategies and improve clinical management.