风险预测模型评估MicroRNA-155对急性髓系白血病患者接受异基因造血干细胞移植不良预后的影响

MicroRNA-155 is a novel prognosticator in acute myeloid leukemia patients undergoing allogeneic hematopoietic stem cell transplantation

目的:分析异基因造血干细胞移植是否能够克服miR-155过表达在急性髓系白血病患者中不良预后影响。方法:筛选癌症基因组图谱(TCGA)数据库中有miRNA表达信息并接受过异基因造血干细胞移植的急性髓系白血病患者,以miR-155表达水平的中位数为临界值将其分为高表达组与低表达组。描述性统计总结两组患者的性别、年龄、染色体核型、预后分组等临床特征及常见基因突变,采用Mann-Whitney U检验、χ2检验、单因素和多因素分析进行比较。结果:除骨髓肿瘤细胞及FLT3-ITD突变、TP53突变外,两组间临床及遗传资料均存在显著差异。两组患者的年龄、性别、白细胞计数、外周血肿瘤细胞百分率、FAB分型等临床特征差异均无统计学意义。单因素分析发现,miR-155高表达OS降低,PHF6、RUNX1、TP53和MLL-PTD突变患者OS降低。多变量分析表明,miR-155高表达是OS较差的独立因素。结论:miR-155高表达与AML患者接受同种异体造血干细胞移植的不良预后相关,是AML预后不良的生物标志物。

Objective: Acute myeloid leukemia(AML) needs fine risk stratification to get an optimal outcome of patients. MiRNAs have important biological functions and play important roles in pathogenesis and prognosis in AML. Whether the overexpression of miR-155 also predicts poor outcome of AML patients undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT) is still unclear. Methods: We screened the The Cancer Genome Atlas(TCGA) database for AML patients with miRNA expression information and had underwent allo-HSCT. The expression levels of miRNA, clinical and molecular information of these AML patients were publicly accessible from the TCGA database. The patients were divided into two groups based on the median expression of miR-155.The clinical and molecular characteristics were summarized with descriptive statistics. The Mann-Whitney U test, the chi-square test,univariate and multivariate analyseswere used. Results: Except for BM blasts, FLT3-ITD mutations and TP53 mutations, there were no significant differences in clinical and genetic data between the two groups. By univariate analyses we identified high expression of miR-155 was unfavorable for OS, mutations in PHF6 、RUNX1、TP53and MLL-PTD negatively affected OS. Further multivariate analyses indicated that high expression of miR-155 was an independent factor for poor OS. Conclusion: High miR-155 expression also correlates with poor prognosis in AML patients undergoing allo-HSCT, like it is regarded as a biomarker for poor prognosis in AML.