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在急性髓细胞白血病中,miR-425 的表达谱分析可能有助于指导异基因移植和化疗之间的治疗选择。

MiR-425 expression profiling in acute myeloid leukemia might guide the treatment choice between allogeneic transplantation and chemotherapy.

机构信息

Blood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.

Department of Hematology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.

出版信息

J Transl Med. 2018 Oct 1;16(1):267. doi: 10.1186/s12967-018-1647-8.

Abstract

BACKGROUND

Acute myeloid leukemia (AML) is a highly heterogeneous disease. MicroRNAs function as important biomarkers in the clinical prognosis of AML.

METHODS

This study identified miR-425 as a prognostic factor in AML by screening the TCGA dataset. A total of 162 patients with AML were enrolled for the study and divided into chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT) groups.

RESULTS

In the chemotherapy group, patients with high miR-425 expression had significantly longer overall survival (OS) and event-free survival (EFS) compared with patients with low miR-425 expression. In multivariate analyses, high miR-425 expression remained independently predictive of a better OS (HR = 0.502, P = 0.005) and EFS (HR = 0.432, P = 0.001) compared with patients with low miR-425 expression. Then, all patients were divided into two groups based on the median expression levels of miR-425. Notably, the patients undergoing allo-HSCT had significantly better OS (HR = 0.302, P < 0.0001) and EFS (HR = 0.379, P < 0.0001) compared with patients treated with chemotherapy in the low-miR-425-expression group. Mechanistically, high miR-425 expression levels were associated with a profile significantly involved in regulating cellular metabolism. Among these genes, MAP3K5, SMAD2, and SMAD5 were predicted targets of miR-425.

CONCLUSIONS

The expression of miR-425 may be useful in identifying patients in need of strategies to select the optimal therapy between chemotherapy and allo-HSCT treatment regimens. Patients with low miR-425 expression may consider early allo-HSCT.

摘要

背景

急性髓系白血病(AML)是一种高度异质性疾病。miRNA 作为 AML 临床预后的重要生物标志物发挥作用。

方法

本研究通过筛选 TCGA 数据集,确定 miR-425 是 AML 的预后因素。共纳入 162 例 AML 患者,分为化疗组和异基因造血干细胞移植(allo-HSCT)组。

结果

在化疗组中,miR-425 高表达患者的总生存期(OS)和无事件生存期(EFS)显著长于 miR-425 低表达患者。多因素分析显示,miR-425 高表达与 OS(HR=0.502,P=0.005)和 EFS(HR=0.432,P=0.001)的改善独立相关,与 miR-425 低表达患者相比。然后,根据 miR-425 的中位表达水平将所有患者分为两组。值得注意的是,在 miR-425 低表达组中,allo-HSCT 患者的 OS(HR=0.302,P<0.0001)和 EFS(HR=0.379,P<0.0001)显著优于化疗患者。机制上,miR-425 高表达水平与显著参与调节细胞代谢的谱相关。在这些基因中,MAP3K5、SMAD2 和 SMAD5 是 miR-425 的预测靶点。

结论

miR-425 的表达可用于识别需要选择化疗和 allo-HSCT 治疗方案的最佳治疗策略的患者。miR-425 低表达的患者可能需要考虑早期 allo-HSCT。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1dbf/6167790/1e0e6986c7a6/12967_2018_1647_Fig1_HTML.jpg

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