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N-钙黏蛋白是一种新型的预后生物标志物,可驱动结直肠癌的恶性进展。

N-cadherin, a novel prognostic biomarker, drives malignant progression of colorectal cancer.

作者信息

Yan Xuebing, Yan Leilei, Liu Sihong, Shan Zezhi, Tian Yuan, Jin Zhiming

机构信息

Department of Surgery, Sixth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200233, P.R. China.

出版信息

Mol Med Rep. 2015 Aug;12(2):2999-3006. doi: 10.3892/mmr.2015.3687. Epub 2015 Apr 27.

Abstract

Recent studies have indicated that the epithelial-mesenchymal transition (EMT) is a key molecular mechanism involved in the development of colorectal cancer (CRC). N-cadherin is a mesenchymal marker of the EMT and has been closely linked to several human malignancies. However, its role in CRC has remained elusive. In the present study, qRT-PCR and western blot analysis indicated that N-cadherin expression was higher in tumor tissues than in that in their adjacent normal tissues. Immunohistochemical evaluation of N-cadherin and E-cadherin (an epithelial marker of the EMT), indicated that N-cadherin expression was significantly associated with tumor differentiation, tumor size as well as tumor, nodes and metastasis stage. Correlation analysis suggested the expression of N-cadherin was negatively correlated with that of E-cadherin in CRC tissues. Kaplan-Meier analysis indicated that patients with high N-cadherin expression had a significantly lower overall survival and disease-free survival rate than those with low N-cadherin expression, while the opposite was found for E-cadherin. Of note, the present study found that high N-cadherin expression was an independent prognostic factor for CRC. In vitro assays showed that N-cadherin was widely expressed in CRC cell lines and silencing of N-cadherin suppressed the proliferation and migration of the CRC cell line HT-29 by upregulating E-cadherin, suggesting a potential role of N-cadherin in inducing EMT. In conclusion, the present study suggested that N-cadherin has the potential of serving as a novel prognostic predictor and a promising therapeutic target for CRC.

摘要

近期研究表明,上皮-间质转化(EMT)是参与结直肠癌(CRC)发生发展的关键分子机制。N-钙黏蛋白是EMT的间质标志物,与多种人类恶性肿瘤密切相关。然而,其在CRC中的作用仍不明确。在本研究中,qRT-PCR和蛋白质印迹分析表明,N-钙黏蛋白在肿瘤组织中的表达高于其相邻正常组织。对N-钙黏蛋白和E-钙黏蛋白(EMT的上皮标志物)的免疫组织化学评估表明,N-钙黏蛋白的表达与肿瘤分化、肿瘤大小以及肿瘤、淋巴结和转移分期显著相关。相关性分析表明,CRC组织中N-钙黏蛋白的表达与E-钙黏蛋白的表达呈负相关。Kaplan-Meier分析表明,N-钙黏蛋白高表达的患者总生存率和无病生存率显著低于N-钙黏蛋白低表达的患者,而E-钙黏蛋白则相反。值得注意的是,本研究发现高N-钙黏蛋白表达是CRC的独立预后因素。体外试验表明,N-钙黏蛋白在CRC细胞系中广泛表达,沉默N-钙黏蛋白可通过上调E-钙黏蛋白抑制CRC细胞系HT-29的增殖和迁移,提示N-钙黏蛋白在诱导EMT中具有潜在作用。总之,本研究表明N-钙黏蛋白有潜力作为CRC的一种新型预后预测指标和有前景的治疗靶点。

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