Abnormal PTBP1 Expression Sustains the Disease Progression of Multiple Myeloma

Abstract

Multiple myeloma (MM) is a hematopoietic malignancy characterized by heterogeneity, which corresponds to alternative splicing (AS) profiles and disadjust gene expression. Bioinformatics analysis of AS factors possibly related to MM progression identified the polypyrimidine tract binding protein (PTBP1) as candidate. The purpose of this study was to confirm the incidence and prognostic value of PTBP1 in MM patients. Several cohorts of 2971 patients presenting newly diagnosed and relapsed MM were enrolled. Correlations between PTBP1 expression and clinicopathological characteristics, proliferative activity, and response to therapy of myeloma cells were analyzed. Moreover, the effect of PTBP1 on the AS pattern of specific aerobic glycolysis-related genes was explored in MM patients. Clinically, PTBP1 expression was present at all stages; it increased with disease progression and poor prognosis, which was even stronger elevated in patients with high tumor burden and drug resistance. Mechanistically, PTBP1 modulated AS of PKM2 and aerobic glycolysis-related genes in MM patients, which play synergistic or additive effects in clinical outcome. PTBP1 may be a novel marker for prognostic prediction and a promising therapeutic target for the development of anti-MM treatments.