Blood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Department of Hematology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
J Transl Med. 2018 Oct 1;16(1):267. doi: 10.1186/s12967-018-1647-8.
Acute myeloid leukemia (AML) is a highly heterogeneous disease. MicroRNAs function as important biomarkers in the clinical prognosis of AML.
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.
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.
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.
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。
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。
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。
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。