Increased Numb protein expression predicts poor clinical outcomes in esophageal squamous cell carcinoma patients
Increased Numb protein expression predicts poor clinical outcomes in esophageal squamous cell carcinoma patients
复制标题
Numb 蛋白表达增加预示食管鳞状细胞癌患者临床结果不佳
DOI：
10.1080/15384047.2016.1276131
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发表时间：
2018-01-01
影响因子：
3.6
通讯作者：
Cheng, Chao
中科院分区：
文献类型：
--
作者：
Liu, Zhenguo;Luo, Canqiao;Cheng, Chao
摘要Numb是一种蛋白质，其在细胞分裂期间的不对称分离决定细胞命运，并且具有与多个研究领域相关的许多功能，包括发育神经生物学和癌症生物学。关于Numb在食管鳞状细胞癌（ESCC）中的作用知之甚少，ESCC是亚洲人群中主要的组织学食管癌。本研究旨在探讨Numb在食管鳞癌中的表达及其生物学功能。从212例患者的组织微阵列分析中发现，与相应的非癌组织相比，Numb在ESCC组织中显著上调。Kaplan-Meier生存分析表明，Numb的高表达与高肿瘤复发率（p = 0.015）和较差的术后总体生存率（p = 0.016）显著相关。采用多元考克斯回归分析，Numb的表达被确定为预后不良的独立预测因子。当使用siRNA敲低ESCC细胞系中的Numb时，存在胱天蛋白酶-3依赖性凋亡和细胞增殖抑制的一致增加，以及癌症干细胞标志物Oct-4、SOX-2和Nanog表达的下调。此外，下调Numb表达与ESCC细胞的迁移没有显著相关。这些结果表明，Numb作为一种癌蛋白，并有可能作为一种新的预后生物标志物和治疗ESCC患者的目标。
ABSTRACT Numb is a protein whose asymmetric segregation during cell division determines cell fate and has numerous functions relevant to multiple fields of study, including developmental neurobiology and cancer biology. Little is known about the role of Numb in esophageal squamous cell carcinoma (ESCC), the predominant histological esophageal carcinoma in Asian populations. In this study, we focused on the expression and biologic functions of Numb in the context of ESCC. From analysis of tissue microarrays with 212 patients, it was found that Numb was significantly upregulated in ESCC tissues compared with corresponding non-cancerous tissues. Kaplan-Meier survival analysis suggests that higher expression of Numb was significantly associated with a high tumor recurrence (p = 0.015) and poor overall post-surgical survival (p = 0.016). Using multiple Cox regression, the expression of Numb was determined to be an independent predictor of poor prognosis. When siRNA was used to knockdown Numb in ESCC cell lines, there was a consistent increase in caspase-3 dependent apoptosis and inhibition of cellular proliferation, as well as downregulation of expression of the cancer stem cell markers Oct-4, SOX-2 and Nanog. In addition, downregulated Numb expression was not significantly associated with the migration of ESCC cells. These results indicate that Numb acts as an oncoprotein and has potential as a novel prognostic biomarker and therapeutic target in ESCC patients.