Department of Pediatrics, Changchun University of Chinese Medicine, Changchun, Jilin 130021, P.R. China.
Oncol Rep. 2019 Jan;41(1):659-667. doi: 10.3892/or.2018.6846. Epub 2018 Nov 2.
B‑precursor acute lymphoblastic leukemia (B‑ALL) is the most common cancer diagnosed in children and adolescents. Despite the fact that the 5‑year survival rate has increased from 60 to 90%, approximately a quarter of children suffer from relapse with poor outcome. To improve the clinical management of B‑ALL, there is an urgent need for prognostic biomarkers for the prediction of B‑ALL outcomes. In the present study, we performed a comprehensive analysis of the gene expression data of 456 samples from five independent cohorts. We first sought to identify B‑ALL‑associated genes by differential gene expression analysis by applying linear models. Then, the statistical modelling was applied to identify candidates related to relapse‑free survival. We identified a total of 1,273 B‑ALL‑associated genes that have functions relevant to chemokine signaling. From these genes, 59 genes were identified as prognostic biomarkers. Based on expression patterns of these genes, we successfully distinguished high‑ and low‑risk groups of B‑ALL patients (log-rank test, P‑value=0.025). We further investigated the 59‑gene expression levels in ALL chemotherapy‑treated cohorts and identified 4 genes as potential drug targets associated with drug sensitivity. Our results provided a novel biomarker panel. By leveraging the large scale of data and statistical modelling, we believe this 59‑gene biomarker could help to unveil the mechanisms underlying B‑ALL progression and become potential drug targets.
B 细胞前体急性淋巴细胞白血病 (B-ALL) 是儿童和青少年中最常见的癌症。尽管 5 年生存率已从 60%提高到 90%,但仍有约四分之一的儿童复发,预后不良。为了改善 B-ALL 的临床管理,迫切需要预测 B-ALL 结局的预后生物标志物。在本研究中,我们对来自五个独立队列的 456 个样本的基因表达数据进行了全面分析。我们首先通过应用线性模型进行差异基因表达分析,试图确定与 B-ALL 相关的基因。然后,我们应用统计建模来识别与无复发生存相关的候选基因。我们总共确定了 1273 个与 B-ALL 相关的基因,这些基因的功能与趋化因子信号有关。在这些基因中,有 59 个被鉴定为预后生物标志物。基于这些基因的表达模式,我们成功地区分了 B-ALL 患者的高风险和低风险组(对数秩检验,P 值=0.025)。我们进一步研究了 ALL 化疗治疗队列中 59 个基因的表达水平,并确定了 4 个基因作为与药物敏感性相关的潜在药物靶点。我们的结果提供了一个新的生物标志物面板。通过利用大规模数据和统计建模,我们相信这个 59 个基因的生物标志物可以帮助揭示 B-ALL 进展的机制,并成为潜在的药物靶点。