Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan.
Leukemia. 2015 May;29(5):1051-9. doi: 10.1038/leu.2014.333. Epub 2014 Nov 27.
As a highly heterogeneous disease, acute myeloid leukemia (AML) needs fine risk stratification to get an optimal outcome of patients. MicroRNAs have florid biological functions and have critical roles in the pathogenesis and prognosis in AML. Expression levels of some single microRNAs are influential for prognosis, but a system integrating several together and considering the weight of each should be more powerful. We thus analyzed the clinical, genetic and microRNA profiling data of 138 de novo AML patients of our institute. By multivariate analysis, we identified that high expression of hsa-miR-9-5p and hsa-miR-155-5p were independent poor prognostic factors, whereas that of hsa-miR-203 had a trend to be a favorable factor. We constructed a scoring system from expression of these three microRNAs by considering the weight of each. The scores correlated with distinct clinical and biological features and outperformed single microRNA expression in prognostication. In both ours and another validation cohort, higher scores were associated with shorter overall survival, independent of other well-known prognostic factors. By analyzing the mRNA expression profiles, we sorted out several cancer-related pathways highly correlated with the microRNA prognostic signature. We conclude that this 3-microRNA scoring system is simple and powerful for risk stratification of de novo AML patients.
作为一种高度异质性的疾病，急性髓系白血病（AML）需要精细的风险分层，以获得患者的最佳治疗效果。microRNAs 具有丰富的生物学功能，在 AML 的发病机制和预后中起着关键作用。一些单个 microRNAs 的表达水平对预后有影响，但整合多个 microRNAs 并考虑每个 microRNAs 的权重应该更有说服力。因此，我们分析了我们机构的 138 例初诊 AML 患者的临床、遗传和 microRNA 分析数据。通过多变量分析，我们确定 hsa-miR-9-5p 和 hsa-miR-155-5p 的高表达是独立的不良预后因素，而 hsa-miR-203 的表达则有成为有利因素的趋势。我们通过考虑每个 microRNAs 的权重，从这些三个 microRNAs 的表达构建了一个评分系统。该评分与不同的临床和生物学特征相关，在预后方面优于单个 microRNA 表达。在我们自己的队列和另一个验证队列中，较高的分数与较短的总生存期相关，与其他众所周知的预后因素无关。通过分析 mRNA 表达谱，我们梳理出与 microRNA 预后特征高度相关的几个癌症相关途径。我们的结论是，这个三 microRNAs 评分系统对于初诊 AML 患者的风险分层简单而强大。
