Prognostic value of the FUT family in acute myeloid leukemia
Prognostic value of the FUT family in acute myeloid leukemia
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DOI：
10.1038/s41417-019-0115-9
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发表时间：
2020-02-01
影响因子：
6.4
通讯作者：
Fu, Lin
中科院分区：
文献类型：
--
作者：
Dai, Yifeng;Cheng, Zhiheng;Fu, Lin
近年来，基因异常越来越多地被视为急性髓细胞白血病（AML）的预后标志。岩藻糖基化是一种广泛存在于癌细胞中的翻译后修饰，由岩藻糖基转移酶（FUTs）催化。然而，FUT家族（FUT 1 -11）在AML中的表达和临床意义尚未研究。从癌症基因组图谱数据库中，共有155例具有完整临床特征和FUT 1 -11表达数据的AML患者纳入我们的研究。在单纯化疗患者中，FUT 3、FUT 6和FUT 7的高表达对无事件生存期（EFS）和总生存期（OS）有不利影响（均P < 0.05），而FUT 4的高表达对EFS和OS有有利影响（均P < 0.01）。然而，在异基因造血干细胞移植（allo-HSCT）组中，我们仅发现高表达和低表达FUT 3亚组之间的EFS存在显著差异（P = 0.047），而其他FUT成员对生存期没有影响。多因素分析证实FUT 4高表达是两种EFS的独立有利预后因素，（HR = 0.423，P = 0.001）和OS（HR = 0.398，P < 0.001），而FUT 6高表达是两种EFS的独立危险因素单纯化疗组的HR为1.871，P = 0.017，OS为1.729，P = 0.028。FUT 4低表达和FUT 6高表达患者的EFS和OS最短（P < 0.05）。FUT 3/6/7高表达提示AML预后不良，FUT 4高表达提示AML预后良好，其中FUT 6和FUT 4的预后最好，但其作用可被allo-HSCT所中和。
Genetic abnormalities are more frequently viewed as prognostic markers in acute myeloid leukemia (AML) in recent years. Fucosylation, catalyzed by fucosyltransferases (FUTs), is a post-translational modification that widely exists in cancer cells. However, the expression and clinical implication of the FUT family (FUT1-11) in AML has not been investigated. From the Cancer Genome Atlas database, a total of 155 AML patients with complete clinical characteristics and FUT1-11 expression data were included in our study. In patients who received chemotherapy alone showed that high expression levels of FUT3, FUT6, and FUT7 had adverse effects on event-free survival (EFS) and overall survival (OS) (all P < 0.05), whereas high FUT4 expression had favorable effects on EFS and OS (all P < 0.01). However, in the allogeneic hematopoietic stem cell transplantation (allo-HSCT) group, we only found a significant difference in EFS between the high and low FUT3 expression subgroups (P = 0.047), while other FUT members had no effect on survival. Multivariate analysis confirmed that high FUT4 expression was an independent favorable prognostic factor for both EFS (HR = 0.423, P = 0.001) and OS (HR = 0.398, P < 0.001), whereas high FUT6 expression was an independent risk factor for both EFS (HR = 1.871, P = 0.017) and OS (HR = 1.729, P = 0.028) in patients who received chemotherapy alone. Moreover, we found that patients with low FUT4 and high FUT6 expressions had the shortest EFS and OS (P < 0.05). Our study suggests that high expressions of FUT3/6/7 predict poor prognosis, high FUT4 expression indicates good prognosis in AML; FUT6 and FUT4 have the best prognosticating profile among them, but their effects could be neutralized by allo-HSCT.