Huang Yan, Li Jiazheng, Chen Yanxin, Jiang Peifang, Wang Lingyan, Hu Jianda
Fujian Provincial Key Laboratory of Hematology, Fujian Institute of Hematology, Fujian Medical University Union Hospital, Fuzhou, China.
Front Oncol. 2020 Sep 29;10:565455. doi: 10.3389/fonc.2020.565455. eCollection 2020.
Over the past 50 years, great progress has been made in the diagnosis and treatment of acute lymphoblastic leukemia (ALL), especially in pediatric patients. However, early recurrence is still an important threat to the survival of patients. In this study, we used integrated bioinformatics analysis to look for biomarkers of early recurrence of B-cell ALL (B-ALL) in childhood and adolescent patients. Firstly, we obtained gene expression profiles from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database and the Gene Expression Omnibus (GEO) database. Then, we identified differentially expressed genes (DEGs) based on whether the disease relapsed early. LASSO and Cox regression analysis were applied to identify a subset of four genes: , S100A10, and A genetic risk score model was constructed based on these four optimal prognostic genes. Time-dependent receiver operating characteristic (ROC) curves were used to evaluate the predictive value of this prognostic model (3-, 5-, and 10-year AUC values >0.7). The risk model was significantly associated with overall survival (OS) and event-free survival in B-ALL (all < 0.0001). In addition, a high risk score was an independent poor prognostic risk factor for OS ( < 0.001; HR = 3.396; 95% CI: 2.387-4.832). Finally, the genetic risk model was successfully tested in B-ALL using an external validation set. The results suggested that this model could be a novel predictive tool for early recurrence and prognosis of B-ALL.
在过去50年里,急性淋巴细胞白血病(ALL)的诊断和治疗取得了巨大进展,尤其是在儿科患者中。然而,早期复发仍然是患者生存的重要威胁。在本研究中,我们使用综合生物信息学分析来寻找儿童和青少年B细胞ALL(B-ALL)早期复发的生物标志物。首先,我们从治疗应用研究以生成有效治疗方法(TARGET)数据库和基因表达综合数据库(GEO)中获取基因表达谱。然后,我们根据疾病是否早期复发来鉴定差异表达基因(DEG)。应用LASSO和Cox回归分析来鉴定四个基因的子集: ,S100A10和 基于这四个最佳预后基因构建了遗传风险评分模型。使用时间依赖性受试者工作特征(ROC)曲线来评估该预后模型的预测价值(3年、5年和10年AUC值>0.7)。该风险模型与B-ALL的总生存期(OS)和无事件生存期显著相关(所有 <0.0001)。此外,高风险评分是OS的独立不良预后风险因素( <0.001;HR = 3.396;95% CI:2.387-4.832)。最后,使用外部验证集在B-ALL中成功测试了遗传风险模型。结果表明,该模型可能是一种用于B-ALL早期复发和预后的新型预测工具。