Overexpression of EPS8 is associated with poor prognosis in patients with acute lymphoblastic leukemia
Overexpression of EPS8 is associated with poor prognosis in patients with acute lymphoblastic leukemia
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EPS8过度表达与急性淋巴细胞白血病患者预后不良相关
DOI：
10.1016/j.leukres.2015.03.007
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发表时间：
2015-06-01
影响因子：
2.7
通讯作者：
Li, Yu-hua
中科院分区：
文献类型：
--
作者：
He, Ying-zhi;Liang, Zhao;Li, Yu-hua
分子标记已成为监测疾病状态的宝贵工具，特别是白血病，因为骨髓样本可以很容易地收集，以便在疾病发展的各个阶段进行分析，包括诊断、治疗和随访。两种已被用作急性白血病预后标志物的基因是Wilms' tumor （WT1）和multidrug - resistant -1 （MDR1）。表皮生长因子受体途径底物8 （EPS8）是一种新基因，在某些实体瘤类型中经常过度表达并与不良预后相关。然而，EPS8是否也与急性淋巴细胞白血病（ALL）的发生有关尚不清楚。本研究采用实时荧光定量PCR检测成人ALL患者（n = 107）和非白血病对照组（n = 22）骨髓样本中EPS8、MDR1和WT1的表达。在ALL患者中均检测到EPS8、MDR1和WT1， EPS8与MDR1、EPS8与WT1、MDR1与WT1的表达谱存在显著相关性。一般来说，患者中EPS8、MDR1或WT1的高表达与较高的复发风险相关。此外，当患者根据基因的高表达或低表达进行分层时，Kaplan-Meier生存分析表明，高eps8 /高wt1 /高mdr1谱的患者的无病生存期明显短于低eps8 /低wt1 /低mdr1谱的患者或被排除在这两组之外的患者（P < 0.0001）。因此，EPS8作为MDR1和WT1，可能是评估ALL患者预后的临床有价值的生物标志物。(C) 2015 Elsevier Ltd.版权所有。
Molecular markers have become an invaluable tool in monitoring disease status particularly of leukemias, as bone marrow samples can be easily collected for analysis during all stages of disease development including diagnosis, treatment, and follow-up. Two genes that have been used as prognostic markers in acute leukemia are Wilms' tumor (WT1) and multidrug resistance-1 (MDR1). A novel gene, epidermal growth factor receptor pathway substrate 8 (EPS8), is often over-expressed and associated with poor outcome in some solid tumor types. However, whether EPS8 is also associated with the development of acute lymphoblastic leukemia (ALL) is unclear. Here, quantitative real-time PCR was used to evaluate the expression of EPS8, MDR1, and WT1 in bone marrow samples of adult ALL patients (n = 107) and non-leukemia controls (n = 22). EPS8, MDR1, and WT1 were detected in ALL patients, and significant correlations were found between expression profiles for EPS8 and MDR1, EPS8 and WT1, and MDR1 and WT1. In general, high expression of EPS8, MDR1, or WT1 in patients was associated with a higher risk of relapse. Furthermore, when patients were stratified based on high or low expression of the genes, Kaplan-Meier survival analysis indicated that disease-free survival of patients with the high-EPS8/high-WT1/highMDR1 profile was significantly shorter than in patients with the low-EPS8/low-WT1/low-MDR1 profile or those excluded from either of these groups (P < 0.0001). Thus, EPS8, as MDR1 and WT1, may be a clinically valuable biomarker for assessing the outcome of ALL patients. (C) 2015 Elsevier Ltd. All rights reserved.