Low expression ofCTBP2andCASP8AP2predicts risk of relapse in childhood B-cell precursor acute lymphoblastic leukemia: a retrospective cohort study
Low expression ofCTBP2andCASP8AP2predicts risk of relapse in childhood B-cell precursor acute lymphoblastic leukemia: a retrospective cohort study
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CTBP2和CASP8AP2的低表达可预测儿童B细胞前体急性淋巴细胞白血病的复发风险：一项回顾性队列研究
DOI：
10.1080/08880018.2020.1798572
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发表时间：
2020
影响因子：
1.7
通讯作者：
Li Zhi-Gang
中科院分区：
文献类型：
--
作者：
Cui Lei;Gao Chao;Wang Chan-Juan;Liu Shu-Guang;Wu Min-Yuan;Zhang Rui-Dong;Li Zhi-Gang
CtBP是一种已知的辅抑制因子，在癌症中大量表达，并调节参与癌症起始、进展和转移的基因。本研究旨在探讨CTBP 2表达在B细胞前体急性淋巴细胞白血病（BCP-ALL）患儿队列中的预后意义。进一步评价CTBP 2和CASP 8AP 2联合表达在BCP-ALL复发风险中的作用。采用qRT-PCR方法检测104例初诊BCP-ALL患儿骨髓CTBP 2 mRNA的表达，同时检测100例BCP-ALL患儿CASP 8AP 2的表达。受试者工作特征（ROC）曲线分析确定CTBP 2和CASP 8AP 2表达的临界值对BCP-ALL复发有良好的预测意义。与CTBP 2高表达患者相比，CTBP 2低表达患者的无复发生存期（RFS）和无事件生存期（EFS）较差。CTBP 2表达水平与CASP 8AP 2表达水平显著相关（r= 0.449，P < 0.001）。根据两种基因表达的综合评价将患者分为3组，同时低表达的患者预后最差（6年RFS：64.6%± 12.8%，P < 0.001）。多因素分析显示CTBP 2、CASP 8AP 2表达、33 d微小残留病（MRD）仍是RFS的独立预后因素。在最终的考克斯风险模型的基础上，我们提出了一种计算风险指数的算法，该算法对预测复发更为精确。总之，CTBP 2和CASP 8AP 2的低表达与儿童BCP-ALL的不良结局和复发风险相关。
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 ofCTBP2expression in a cohort of pediatric patients with B cell precursor acute lymphoblastic leukemia (BCP-ALL). It further evaluated the role of combinedCTBP2andCASP8AP2expression in risk of relapse of BCP-ALL. The expression ofCTBP2mRNA was retrospectively detected by a qRT-PCR approach in bone marrow samples from 104 children with newly diagnosed BCP-ALL.CASP8AP2was assessed simultaneously in the 100 patients included in this study. The receiver operating characteristic (ROC) curve analysis determined the cut off levels forCTBP2andCASP8AP2expression with good predictive significance for relapse of BCP-ALL. Patients with lowCTBP2expression had inferior relapse-free survival (RFS) and event-free survival (EFS) when compared to patients with high-CTBP2expression. The expression level ofCTBP2was significantly associated withCASP8AP2expression (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 ofCTBP2andCASP8AP2, 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 ofCTBP2andCASP8AP2correlated with poor outcome and predicted risk of relapse in pediatric BCP-ALL.