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N-钙黏蛋白表达降低与肝癌的转移潜能和手术预后不良相关。

Reduced N-cadherin expression is associated with metastatic potential and poor surgical outcomes of hepatocellular carcinoma.

机构信息

Department of Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

J Gastroenterol Hepatol. 2012 Jan;27(1):173-80. doi: 10.1111/j.1440-1746.2011.06847.x.

DOI:10.1111/j.1440-1746.2011.06847.x
PMID:21777276
Abstract

BACKGROUND AND AIM

N-cadherin (N-cad), one of the classic cadherins, has been reported to be involved in tumor metastasis in some types of tumors. This study aims to investigate the expression status of N-cad in hepatocellular carcinoma (HCC) and the correlation between N-cad expression and metastatic potential, as well as the surgical outcomes of HCC.

METHODS

N-cad expression in HCC and adjacent liver tissues, as well as normal liver tissues, was studied by immunohistochemistry and Western blot, and the relationship between N-cad expression and the clinicopathological features of HCC was evaluated. By using RNA interference technique, the correlation of N-cad expression and metastatic potential was investigated by downregulating N-cad expression in HCCLM3 cells, and the effects of N-cad downregulation on cell aggregation, migration, and invasion were then analyzed. Furthermore, the correlation between N-cad expression and the surgical outcomes of a cohort of HCC patients was analyzed.

RESULTS

In liver tissues, N-cad was strongly expressed on cell-cell boundaries, whereas various reduced-expression patterns were observed in tumors. Of 64 HCC, 34 (53%) tumors showed reduced N-cad expression, compared with their adjacent liver tissues. The decreased expression of N-cad was significantly correlated with poorer tumor differentiation (P = 0.001) and vascular invasion (P = 0.003). N-cad knockdown in HCCLM3 cells resulted in decreased cell aggregation and increased cell migration and invasion. The decreased expression of N-cad in HCC was significantly associated with shorter postoperative disease-free survival (P = 0.039).

CONCLUSIONS

N-cad expression is decreased in HCC, and the downregulation of N-cad is associated with the metastatic potential of HCC and poorer surgical prognosis.

摘要

背景与目的

N-钙黏蛋白(N-cad)是经典钙黏蛋白家族中的一员,已有研究报道其在某些类型的肿瘤中与肿瘤转移有关。本研究旨在探讨 N-cad 在肝细胞癌(HCC)中的表达状态及其与转移潜能的相关性,以及与 HCC 手术预后的关系。

方法

采用免疫组织化学和 Western blot 检测 HCC 及其相邻肝组织、正常肝组织中 N-cad 的表达,并评估 N-cad 表达与 HCC 临床病理特征的关系。采用 RNA 干扰技术下调 HCCLM3 细胞中 N-cad 的表达,探讨 N-cad 表达与转移潜能的相关性,并分析 N-cad 下调对细胞聚集、迁移和侵袭的影响。进一步分析 N-cad 表达与一组 HCC 患者手术预后的关系。

结果

在肝组织中,N-cad 在细胞-细胞边界处强表达,而在肿瘤中观察到各种低表达模式。在 64 例 HCC 中,有 34 例(53%)肿瘤的 N-cad 表达降低,与相邻肝组织相比。N-cad 表达降低与肿瘤分化较差(P = 0.001)和血管侵犯(P = 0.003)显著相关。下调 HCCLM3 细胞中的 N-cad 表达导致细胞聚集减少,而迁移和侵袭增加。N-cad 在 HCC 中的低表达与术后无病生存时间较短显著相关(P = 0.039)。

结论

N-cad 在 HCC 中表达降低,下调 N-cad 与 HCC 的转移潜能和较差的手术预后相关。

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