Spliced X-Box binding protein 1 predicts satisfying responsiveness and survival benefit toward bortezomib-based therapy in multiple myeloma patients

Abstract

Objective: Spliced X-Box binding protein 1 (sXBP1) modulates malignant cell activities and enhances the bortezomib sensitivity in multiple myeloma (MM) cells, while its clinical value in MM patients remains elusive. Hence, the current study aimed to explore this issue, particularly the correlation of sXBP1 with treatment outcomes of bortezomib-based therapy in MM patients. Methods: Totally, 97 newly-diagnosed MM patients undergoing bortezomib-based therapy, 20 disease controls (DCs), and 20 health controls (HCs) were enrolled. Bone marrow plasma cell samples were acquired to determine sXBP1 by RT-qPCR. Results: sXBP1 was lowest in MM patients, followed by DCs, and highest in HCs (P < 0.001). Beyond that, sXBP1 discriminated MM patients from DCs with area under curve (AUC) of 0.728 (95% confidence interval (CI): 0.610–0.847) and HCs with AUC of 0.855 (95% CI: 0.771–0.939). sXBP1 was negatively associated with t (4; 14) (P = 0.047), Revised International Staging System stage (P = 0.008). There was a trend that sXBP1 was negatively correlated with β2-MG, LDH, and t (14; 16) (without statistical significance). sXBP1 was higher in patients with complete response (CR) compared to those with non-CR (P = 0.017) and higher in patients with objective response rate (ORR) compared to those with non-ORR (P = 0.006). sXBP1 (high vs. low) was linked with longer progression-free survival (PFS) (P = 0.011) and overall survival (P = 0.045) in MM patients. Additionally, sXBP1 (high vs. low) (P = 0.025) independently estimated a longer PFS. Conclusion: sXBP1 forecasts a favorable treatment response and survival benefit toward bortezomib-based therapy in multiple myeloma patients.