A 4‐microRNA signature for survival prognosis in pediatric and adolescent acute myeloid leukemia
A 4‐microRNA signature for survival prognosis in pediatric and adolescent acute myeloid leukemia
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DOI：
10.1002/jcb.27679
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发表时间：
2018-09
影响因子：
4
通讯作者：
Ruiqi Zhu;Wen-yi Lin;Wei-wei Zhao;Fengjuan Fan;L. Tang;Yu Hu
中科院分区：
文献类型：
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作者：
Ruiqi Zhu;Wen-yi Lin;Wei-wei Zhao;Fengjuan Fan;L. Tang;Yu Hu
急性髓系白血病（AML）是一种具有明显分子异质性的血液系统恶性肿瘤。microRNA（miRNAs）在AML的诊断、发病机制和预后中起着关键作用。在儿童和青少年患者中识别miRNA特征以预测总生存率方面所做的工作很少。本研究旨在通过分析来自癌症基因组图谱（TCGA）的数据，确定一组可以预测所有AML亚型的所有年轻AML患者预后的miRNA特征。共有229例年龄在23岁以下的患者入组本研究，这些患者具有来自TCGA数据库的miRNA数据和相应的临床数据。在训练试验中进行多因素分析，发现hsa-miR-509和hsa-miR-542的高表达是独立的不良预后因素，而hsa-miR-146 a和hsa-miR-3667的高表达有成为有利因素的趋势。考虑到每个miRNA的权重，通过这些miRNA构建4-miRNA签名。在测试组和所有229名患者队列以及59名细胞遗传学正常的AML（CN-AML）患者队列中，较高的风险评分与较短的总生存期（OS）相关。所有结果均通过强大的统计分析保密。进行了基因本体论和京都基因百科全书和基因组分析，以进一步开发支持该模型的白血病相关机制。结果表明，基于4-miRNA的特征是儿童和青少年AML患者的可靠预后生物标志物。
Acute myeloid leukemia (AML) is a hematologic malignancy with significant molecular heterogeneity. MicroRNAs (miRNAs) play a critical role in AML diagnosis, pathogenesis, and prognosis of AML. Little has been done to identify a miRNA signature in pediatric and adolescent patients for predicting overall survival. This study aims to identify a panel of miRNA signature that could predict the prognosis of all younger AML patients with all subtypes of AML by analyzing data from The Cancer Genome Atlas (TCGA). A total of 229 patients under 23 years with miRNA data and corresponding clinical data from TCGA database were enrolled in this study. Through conducting multivariate analysis in the training test, it was identified that the high expression of hsa‐miR‐509 and hsa‐miR‐542 were independent poor prognostic factors, whereas that of hsa‐miR‐146a and hsa‐miR‐3667 had a trend to be favorable factors. A 4‐miRNA signature was constructed by these miRNAs considering the weight of each. In testing group and all 229 patients’ cohort as well as 59 cytogenetically normal AML (CN‐AML) patients’ cohort, higher risk score was associated with shorter overall survival (OS). All results were confidential by using powerful statistical analysis. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis were carried out to further develop leukemia‐relevant mechanisms supporting the model. The results indicate that the 4‐miRNA‐based signature is a reliable prognostic biomarker for pediatric and adolescent AML patients.