Zhang Nan, Chen Ying, Lou Shifeng, Shen Yan, Deng Jianchuan
Department of Hematology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, People's Republic of China.
Onco Targets Ther. 2019 Aug 16;12:6591-6604. doi: 10.2147/OTT.S218928. eCollection 2019.
Acute myeloid leukemia (AML) is a malignant clonal disorder. Despite enormous progress in its diagnosis and treatment, the mortality rate of AML remains high. The aim of this study was to identify prognostic biomarkers by using the gene expression profile dataset from public database, and to improve the risk-stratification criteria of survival for patients with AML.
The gene expression data and clinical parameter were acquired from the Therapeutically Applicable Research to Generate Effective Treatment (TARGET) database. A total of 856 differentially expressed genes (DEGs) were obtained from the childhood AML patients classified into first complete remission (CR1) group (n=791) and not CR group (n=249). We performed a series of bioinformatics analysis to screen key genes and pathways, further comprehending these DEGs through Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses.
Six genes ( and ) identified by univariate, Kaplan-Meier survival and multivariate Cox regression analyses were used to develop the prognostic model. Further analysis showed that the survival estimations in the high-risk group had an increased risk of death compared with the low-risk group based on the model. The area under the curve of the receiver operator characteristic curve in the prognostic model for predicting the overall survival was 0.729, confirming good prognostic model. We also performed a nomogram to provide an individual patient with the overall probability, and internal validation in the TARGET cohort.
We identified a six-gene prognostic signature for risk-stratifying in patients with childhood AML. The risk classification model can be used to predict CR markers and may assist clinicians in providing realize the individualized treatment in this patient population.
急性髓系白血病(AML)是一种恶性克隆性疾病。尽管其诊断和治疗取得了巨大进展,但AML的死亡率仍然很高。本研究的目的是利用公共数据库中的基因表达谱数据集识别预后生物标志物,并改善AML患者生存的风险分层标准。
从治疗应用研究以产生有效治疗(TARGET)数据库中获取基因表达数据和临床参数。从分为首次完全缓解(CR1)组(n = 791)和未缓解组(n = 249)的儿童AML患者中总共获得了856个差异表达基因(DEG)。我们进行了一系列生物信息学分析以筛选关键基因和通路,通过基因本体论(GO)功能和京都基因与基因组百科全书(KEGG)通路分析进一步理解这些DEG。
通过单变量、Kaplan-Meier生存分析和多变量Cox回归分析确定的六个基因用于建立预后模型。进一步分析表明,基于该模型,高风险组的生存估计与低风险组相比死亡风险增加。预测总生存的预后模型中受试者工作特征曲线下面积为0.729,证实了良好的预后模型。我们还制作了列线图以提供个体患者的总体概率,并在TARGET队列中进行了内部验证。
我们为儿童AML患者的风险分层确定了一个六基因预后特征。该风险分类模型可用于预测CR标志物,并可能有助于临床医生在该患者群体中实现个体化治疗。