Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, and Guangzhou Medical University, Guangzhou, China.
Laboratory of RNA, Chromatin and Human Disease, Guangzhou, 510530, China.
Sci Rep. 2020 Feb 26;10(1):3505. doi: 10.1038/s41598-020-60480-x.
WW domain binding protein 5 (WBP5), also known as Transcriptional Elongation Factor A like 9 (TCEAL9) has been proposed as a candidate oncogene for human colorectal cancers with microsatellite instability and as a predictive indicator of small cell lung cancers. Furthermore, several independent studies have proposed WBP5, and its association with Wilms Tumor-1 (WT1) expression, as part of a gene expression-based risk score for predicting survival and clinical outcome in patients with Acute Myeloid Leukaemia (AML). To date, the prognostic significance of the sole WBP5 expression and its impact on the survival outcome in AML patients remains largely understudied. In the present study, we have made use of publicly available patient expression arrays and have developed an unbiased approach to classify AML patients into low versus high WBP5 expressers and to balance them for known mutations and cytogenetic findings. Interestingly, we found that patients characterized by high WBP5 expression displayed inferior overall and event-free survival rates. Notably, gene expression profiling showed that patients with high WBP5 had elevated expression of several HOX cluster genes, such as HOXA5, HOXA7, HOXA9 and HOXA10, and several of their partner proteins, such as MEIS1 and FOXC1, which have been demonstrated to be causative for AML. Taken together, our data suggest that WBP5 expression level could serve as an indicator for prognosis and survival outcome in patients with AML.
WW 结构域结合蛋白 5（WBP5），也称为转录延伸因子 A 样 9（TCEAL9），被提议作为具有微卫星不稳定性的人类结直肠癌的候选癌基因，以及小细胞肺癌的预测指标。此外，几项独立的研究已经提出了 WBP5，及其与肾母细胞瘤-1（WT1）表达的关联，作为基于基因表达的风险评分的一部分，用于预测急性髓系白血病（AML）患者的生存和临床结局。迄今为止，WBP5 表达的单一预后意义及其对 AML 患者生存结局的影响在很大程度上仍未得到充分研究。在本研究中，我们利用了公开的患者表达数组，并采用了一种无偏的方法将 AML 患者分为低表达和高表达 WBP5 的患者，并对已知的突变和细胞遗传学发现进行平衡。有趣的是，我们发现高 WBP5 表达的患者总体和无事件生存率较低。值得注意的是，基因表达谱分析表明，高 WBP5 患者的 HOX 簇基因，如 HOXA5、HOXA7、HOXA9 和 HOXA10，以及它们的几个伴侣蛋白，如 MEIS1 和 FOXC1 的表达水平升高，这些基因和蛋白已被证明是 AML 的致病因素。总之，我们的数据表明，WBP5 表达水平可作为 AML 患者预后和生存结局的指标。
