Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Epidemiology and Biostatistics, School of Public Health, Harbin Medical University, Harbin, China.
J Cell Biochem. 2019 Mar;120(3):3958-3968. doi: 10.1002/jcb.27679. Epub 2018 Sep 22.
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.
急性髓系白血病（AML）是一种具有显著分子异质性的血液系统恶性肿瘤。MicroRNAs（miRNAs）在 AML 的诊断、发病机制和预后中起着关键作用。目前，在儿科和青少年患者中，很少有研究用于确定预测总生存期的 miRNA 特征。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 miRNA 特征，以预测所有年轻 AML 患者（包括所有 AML 亚型）的预后。本研究共纳入了 229 名年龄在 23 岁以下、具有 miRNA 数据和相应临床数据的 TCGA 数据库患者。通过在训练测试中进行多变量分析，确定 hsa-miR-509 和 hsa-miR-542 的高表达是独立的不良预后因素，而 hsa-miR-146a 和 hsa-miR-3667 则有成为有利因素的趋势。考虑到每个 miRNA 的权重，构建了一个由这四个 miRNA 组成的特征。在测试组和所有 229 名患者队列以及 59 名核型正常 AML（CN-AML）患者队列中，风险评分较高与总生存期（OS）较短相关。所有结果均通过强大的统计分析进行保密。进行了基因本体论和京都基因与基因组百科全书分析，以进一步开发支持该模型的与白血病相关的机制。结果表明，基于 4 个 miRNA 的特征是儿科和青少年 AML 患者可靠的预后生物标志物。
