High expression of miR-363 predicts poor prognosis and guides treatment selection in acute myeloid leukemia
High expression of miR-363 predicts poor prognosis and guides treatment selection in acute myeloid leukemia
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miR-363的高表达预示着急性髓系白血病的不良预后并指导治疗选择
DOI：
10.1186/s12967-019-1858-7
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发表时间：
2019
影响因子：
7.4
通讯作者：
Kailin Xu
中科院分区：
文献类型：
--
作者：
Huihui Zhang;Ninghan Zhang;Rong Wang;Tingting Shao;Yuan Feng;Yao Yao;Qingyun Wu;Shengyun Zhu;Jiang Cao;Huanxin Zhang;Zhenyu Li;Xuejiao Liu;Mingshan Niu;Kailin Xu
BackgroundAcute myeloid leukemia（AML）是一种高度异质性的恶性肿瘤，具有多种结局，因此需要更好的风险分层工具来帮助选择最佳的治疗方案MethodsIn this study，we identified miRNAs that could predict clinical outcome in a heterogeneous AML population using TCGA dataset.ResultsWe found MiR-363 is a novel prognostic factor in AML patients undergoing chemotherapy.在多变量分析中，高miR-363仍然预测较短的OS（HR = 2.349，P = 0.012）和EFS（HR = 2.082，P = 0.001），独立于其他众所周知的预后因素。更重要的是，异基因造血干细胞移植（allo-HSCT）克服了与高miR-363表达相关的不良结局。在基因表达谱中，miR-363的高表达与白血病转录因子的量呈正相关，包括Myb、RUNX 3、GATA 3、IKZF 3、ETS 1和MLLT 3。值得注意的是，我们发现，在硅预测的靶基因（EZH 2，KLF 6和PTEN）的miR-363下调与高miR-363 expressions.ConclusionsIn总结，miR-363的表达可能有助于确定患者需要的策略，以选择化疗和allo-HCST方案之间的最佳治疗。miR-363高表达的AML患者可被强烈推荐用于早期allo-HSCT方案。
BackgroundAcute myeloid leukemia (AML) is a highly heterogeneous malignancy with various outcomes, and therefore needs better risk stratification tools to help select optimal therapeutic options.MethodsIn this study, we identify miRNAs that could predict clinical outcome in a heterogeneous AML population using TCGA dataset.ResultsWe found that MiR-363 is a novel prognostic factor in AML patients undergoing chemotherapy. In multivariable analyses, high miR-363 remained predictive for shorter OS (HR = 2.349, P = 0.012) and EFS (HR = 2.082, P = 0.001) independent of other well-known prognostic factors. More importantly, allogeneic hematopoietic stem cell transplantation (allo-HSCT) overcame the adverse outcomes related to high miR-363 expression. In gene expression profiling, high miR-363 expression was positively correlated with the amounts of leukemogenic transcription factors, including Myb, RUNX3, GATA3, IKZF3, ETS1 and MLLT3. Notably, we found that the in silico predicted target genes (EZH2, KLF6 and PTEN) of miR-363 were downregulated in association with high miR-363 expression.ConclusionsIn summary, miR-363 expression may help identify patients in need of strategies to select the optimal therapy between chemotherapeutic and allo-HCST regimens. AML patients with high miR-363 expression may be highly recommended for early allo-HSCT regimen.