Low expression of CTBP2 and CASP8AP2 predicts risk of relapse in childhood B-cell precursor acute lymphoblastic leukemia: a retrospective cohort study.

ABSTRACT

CtBP is a known corepressor abundantly expressed in cancer and regulates genes involved in cancer initiation, progression, and metastasis. This study aimed to investigate the prognostic significance of CTBP2 expression in a cohort of pediatric patients with B cell precursor acute lymphoblastic leukemia (BCP-ALL). It further evaluated the role of combined CTBP2 and CASP8AP2 expression in risk of relapse of BCP-ALL. The expression of CTBP2 mRNA was retrospectively detected by a qRT-PCR approach in bone marrow samples from 104 children with newly diagnosed BCP-ALL. CASP8AP2 was assessed simultaneously in the 100 patients included in this study. The receiver operating characteristic (ROC) curve analysis determined the cut off levels for CTBP2 and CASP8AP2 expression with good predictive significance for relapse of BCP-ALL. Patients with low CTBP2 expression had inferior relapse-free survival (RFS) and event-free survival (EFS) when compared to patients with high-CTBP2 expression. The expression level of CTBP2 was significantly associated with CASP8AP2 expression (r = 0.449, P < 0.001). Patients were stratified into three groups according to the combined evaluation of the two gene expression, and patients with simultaneous low-expression had the worst outcome (6-year RFS 64.6%±12.8%, P < 0.001). Multivariate analysis demonstrated the expression of CTBP2 and CASP8AP2, minimal residual disease (MRD) at day 33 remained as independent prognostic factors for RFS. Based on the final Cox hazards model, we proposed an algorithm to calculate the risk index, which was more precise for predicting relapse. In conclusion, low expression of CTBP2 and CASP8AP2 correlated with poor outcome and predicted risk of relapse in pediatric BCP-ALL.