Integrative meta-analysis of differential gene expression in acute myeloid leukemia.
Integrative meta-analysis of differential gene expression in acute myeloid leukemia.
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DOI：
10.1371/journal.pone.0009466
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发表时间：
2010-03-01
期刊：
影响因子：
3.7
通讯作者：
Stamatoyannopoulos JA
中科院分区：
文献类型：
--
作者：
Miller BG;Stamatoyannopoulos JA
急性髓系白血病(AML)是一种异质性疾病，总体预后较差。AML患者的基因表达谱研究提供了对疾病发病机制的关键见解，同时揭示了潜在的诊断和预后标志物和治疗靶点。对AML中大量的基因表达谱研究进行系统比较，有可能检验基于单一研究的结论的可扩充性，并为AML提供进一步的见解。在这项研究中，我们系统地比较了25个已发表的关于AML基因表达谱的报告。总共报告了4918个基因，其中三分之一是在不止一项研究中报告的。我们发现，在至少一项其他研究中，只有一小部分报告的预后相关基因(9.6%)是重复的。在一项联合分析中，我们全面识别了在不同的预后类别中表现出显著差异调节的基因集和功能基因类别和通路，包括许多以前未报道的关联。我们开发了一种新的方法，对逐个基因的数据及其与既定预后特征和患者预后的关系进行细粒度、交叉研究分析。我们在AML中发现了许多先前研究没有发现的新的预后分子特征，这些特征为AML的发病机制提供了洞察，具有潜在的诊断、预后和治疗意义。我们的数据库和综合分析可在网上获得(http://gat.stamlab.org).
Acute myeloid leukemia (AML) is a heterogeneous disease with an overall poor prognosis. Gene expression profiling studies of patients with AML has provided key insights into disease pathogenesis while exposing potential diagnostic and prognostic markers and therapeutic targets. A systematic comparison of the large body of gene expression profiling studies in AML has the potential to test the extensibility of conclusions based on single studies and provide further insights into AML. In this study, we systematically compared 25 published reports of gene expression profiling in AML. There were a total of 4,918 reported genes of which one third were reported in more than one study. We found that only a minority of reported prognostically-associated genes (9.6%) were replicated in at least one other study. In a combined analysis, we comprehensively identified both gene sets and functional gene categories and pathways that exhibited significant differential regulation in distinct prognostic categories, including many previously unreported associations. We developed a novel approach for granular, cross-study analysis of gene-by-gene data and their relationships with established prognostic features and patient outcome. We identified many robust novel prognostic molecular features in AML that were undetected in prior studies, and which provide insights into AML pathogenesis with potential diagnostic, prognostic, and therapeutic implications. Our database and integrative analysis are available online (http://gat.stamlab.org).
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