Han Qi, Zhang Qi, Song Huihui, Bamme Yevgeniya, Song Chunhua, Ge Zheng
Department of Hematology, Zhongda Hospital, School of Medicine, Southeast University, Institute of Hematology Southeast University, Nanjing, China.
International Cooperative Leukemia Group and International Cooperative Laboratory of Hematology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
Front Oncol. 2020 Feb 27;10:149. doi: 10.3389/fonc.2020.00149. eCollection 2020.
The F-box and WD repeat domain-containing (FBXW) proteins play an important role in ubiquitin proteasome by inducing protein degradation. Ten FBXW proteins have been identified in humans. The functions of FBXW proteins, like FBXW7, have been well-established in many human cancers. However, little is known about their transcriptional expression profiles and relationship with prognosis in acute myeloid leukemia (AML). Here we investigated the roles of FBXW proteins in AML by analyzing their mRNA expression profiles and association with clinical features using data from EMBL-EBI, the Cancer Cell Line Encyclopedia, Gene Expression Profiling Interactive Analysis, and cBioPortal databases. Our results showed that the mRNA level of FBXW proteins were highly detected by microarray in 14 AML cell lines, although there were no obvious differences. The expression of was significantly higher in AML patients compared with that in normal controls ( < 0.01). Patients whose age was ≥60 years old had a higher expression when compared with those who were <60 years old ( < 0.05). Cytogenetic favorable-risk group patients had a much lower expression than the intermediate- and poor-risk group patients ( < 0.0001). Moreover, patients with high expression exhibited significantly shorter event-free survival (EFS) and overall survival (OS) than those with low expression (median EFS: 5.3 vs. 10.0 months, = 0.025; median OS: 8.1 vs. 19.0 months, = 0.015). A multivariate analysis indicated that high expression was an independent risk factor for poor EFS in AML patients who received intensive chemotherapy followed by allo-SCT. In summary, our data suggested that is aberrantly expressed in AML and high expression might be a poor prognostic biomarker; future functional and mechanistic studies will further illuminate the roles of in AML.
含F盒和WD重复结构域（FBXW）的蛋白质通过诱导蛋白质降解在泛素蛋白酶体中发挥重要作用。在人类中已鉴定出10种FBXW蛋白。FBXW蛋白（如FBXW7）的功能在许多人类癌症中已得到充分证实。然而，关于它们在急性髓系白血病（AML）中的转录表达谱及其与预后的关系却知之甚少。在这里，我们通过分析来自欧洲生物信息学研究所（EMBL-EBI）、癌症细胞系百科全书（Cancer Cell Line Encyclopedia）、基因表达谱交互式分析（Gene Expression Profiling Interactive Analysis）和cBioPortal数据库的数据，研究了FBXW蛋白在AML中的作用，分析了它们的mRNA表达谱及其与临床特征的关联。我们的结果表明，通过微阵列在14种AML细胞系中高度检测到FBXW蛋白的mRNA水平，尽管没有明显差异。与正常对照相比，AML患者中[具体蛋白名称未明确给出]的表达显著更高（P<0.01）。年龄≥60岁的患者与年龄<60岁的患者相比，[具体蛋白名称未明确给出]表达更高（P<0.05）。细胞遗传学有利风险组患者的[具体蛋白名称未明确给出]表达远低于中危和高危组患者（P<0.0001）。此外，[具体蛋白名称未明确给出]高表达患者的无事件生存期（EFS）和总生存期（OS）明显短于低表达患者（中位EFS：5.3个月对10.0个月，P = 0.025；中位OS：8.1个月对19.0个月，P = 0.015）。多变量分析表明，高[具体蛋白名称未明确给出]表达是接受强化化疗后进行异基因造血干细胞移植（allo-SCT）的AML患者EFS不良的独立危险因素。总之，我们的数据表明[具体蛋白名称未明确给出]在AML中异常表达，高[具体蛋白名称未明确给出]表达可能是一个不良预后生物标志物；未来的功能和机制研究将进一步阐明[具体蛋白名称未明确给出]在AML中的作用。
