Expression of Lgr5, a marker of intestinal stem cells, in colorectal cancer and its clinicopathological significance
Expression of Lgr5, a marker of intestinal stem cells, in colorectal cancer and its clinicopathological significance
复制标题
肠干细胞标志物Lgr5在结直肠癌中的表达及其临床病理意义
DOI：
10.1016/j.biopha.2014.03.016
复制
发表时间：
2014-06-01
影响因子：
7.5
通讯作者：
Zhang, Yanyun
中科院分区：
文献类型：
--
作者：
He, Songbing;Zhou, Hao;Zhang, Yanyun
肿瘤干细胞（cancer stem cells，CSCs）是近年来肿瘤研究的热点之一，但CSCs的细胞来源尚未明确。Lgr5是Wnt/β-连环蛋白信号传导的调节靶点，其首先被鉴定为肠干细胞的标志物。然而，Lgr5在结直肠癌中的表达及其临床病理意义以及与Wnt/β-catenin通路的相关性尚未完全阐明。免疫组化染色检测大肠癌组织中Lgr 5的定位和表达。分析其表达水平与患者临床病理特征及临床预后的相关性。使用实时RT-PCR测定Lgr5在各种CRC细胞系中的定量表达水平。同时研究大肠癌中Lgr5表达与Wnt/β-catenin通路的关系。与配对的非肿瘤组织相比，在CRC组织中观察到Lgr5的表达明显升高。大肠癌组织中Lgr5 mRNA表达水平与β-catenin表达水平呈正相关。Lgr 5在不同的结直肠癌细胞系中表达不同。Lgr 5的低表达和高表达与结直肠癌患者的临床病理特征如TNM分期、淋巴结转移和血管浸润密切相关。更重要的是，结直肠癌组织中Lgr5的表达也与肿瘤血管生成以及临床结局相关。综上所述，这些结果表明，Lgr 5表达升高可能有助于CRC的发生和进展，并且它也可以用作CRC的潜在不利预后生物标志物。更好地理解Lgr 5在CRC进展中的分子机制和潜在价值的相关性将有助于为CRC患者确定新的治疗策略。(C)2014年Elsevier Masson SAS。All rights reserved.
Cancer stem cells (CSCs) have been the focus of intense investigations in cancer research although the cellular origin of CSCs has not been clearly determined. Lgr5 is a regulated target of Wnt/beta-catenin signaling, which was first identified as a marker of intestinal stem cells. However, the expression of Lgr5 in human colorectal cancer (CRC) and its clinical clinicopathological significance in CRC patients as well as its correlation with Wnt/beta-catenin pathway are not fully explored. Localization and expression of Lgr5 in CRC tissues was performed by immunohistochemical staining. The correlation between its expression levels and clinicopathological features as well as clinical outcomes of patients was analysed. The quantitative expression levels of Lgr5 in various CRC cell lines were determined using real-time RT-PCR. The relationship between Lgr5 expression and Wnt/beta-catenin pathway in CRC was also investigated. Obviously elevated expression of Lgr5 was observed in CRC tissues, compared to the paired nontumor tissues. mRNA expression levels of Lgr5 was positively correlated with the expression of beta-catenin in CRC tissues. The expression of Lgr5 was various in different CRC cell lines. Low and high expression levels of Lgr5 were significantly correlated with clinicopathological features such as TNM stage, lymph node metastasis and vascular invasion of CRC patients. More importantly, Lgr5 expression in CRC tissues was also associated with tumor angiogenesis as well as clinical outcomes. Taken together, these results suggest that elevated Lgr5 expression might contribute to the development and progression of CRC, and it could also be used a potential unfavorable prognostic biomarker for CRC. A better understanding of molecule mechanisms and the relevance of potential value for Lgr5 in the progression of CRC will help to identify a novel therapeutic strategy for CRC patients. (C) 2014 Elsevier Masson SAS. All rights reserved.