Overexpression of WAVE3 promotes tumor invasiveness and confers an unfavorable prognosis in human hepatocellular carcinoma
Overexpression of WAVE3 promotes tumor invasiveness and confers an unfavorable prognosis in human hepatocellular carcinoma
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DOI：
10.1016/j.biopha.2014.11.001
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发表时间：
2015-02-01
影响因子：
7.5
通讯作者：
Zhang, Wenjin
中科院分区：
文献类型：
--
作者：
Ji, Yingjie;Li, Bing;Zhang, Wenjin
背景：Wiskott-Aldrich 综合征 verprolin-homologous (WAVE) 3 据报道与多种恶性肿瘤有关，但其在肝细胞癌 (HCC) 中的作用仍不清楚。本研究的目的是探讨WAVE3对HCC细胞行为的影响并评估其临床影响。材料与方法：采用免疫组化法检测120对HCC及癌旁非癌组织中WAVE3的表达模式。然后，检查了 WAVE3 表达与临床病理特征和患者预后的关系。体外评估了WAVE3在HCC细胞系HepG2迁移和侵袭中的作用。结果：WAVE3蛋白的阳性免疫染色主要出现在HCC细胞的细胞质中。与癌旁非癌组织相比，HCC组织中WAVE3蛋白的表达水平显着上调（P < 0.001）。此外，WAVE3 高表达与晚期肿瘤分期 (P = 0.008) 和阳性远处转移 (P = 0.001) 显着相关。然后，WAVE3 高表达与不良预后显着相关，并且 WAVE3 状态被确定为独立的重要预后因素。此外，使用靶向WAVE3的小干扰RNA来抑制HepG2细胞中WAVE3的表达。我们发现抑制WAVE3可以抑制HepG2细胞的迁移和侵袭。结论：我们的临床研究将WAVE3描述为HCC进展和转移的生物标志物，更重要的是，将其确定为HCC患者的独立预后标志物。我们的数据还表明，WAVE3 对于控制人类 HCC 细胞的致癌表型至关重要。 (C) 2014 年由 Elsevier Masson SAS 出版。
Background: Wiskott-Aldrich syndrome verprolin-homologous (WAVE) 3 has been reported to be implicated in various malignant tumors, but its role in hepatocellular carcinoma (HCC) remains elusive. The aim of this study was to investigate the effect of WAVE3 on the behaviors of HCC cells and to evaluate its clinical impact.Materials and methods: A total of 120 paired of HCC and adjacent non-cancerous tissues were used to detect expression pattern of WAVE3 by immunohistochemistry. Then, the associations of WAVE3 expression with clinicopathologic characteristics and patients' prognosis were examined. The roles of WAVE3 in migration and invasion of HCC cell line HepG2 were also evaluated in vitro.Results: Positive immunostaining of WAVE3 protein was predominantly observed in the cytoplasm of HCC cells. Compared to adjacent non-cancerous tissues, the expression levels of WAVE3 protein were significantly upregulated in HCC tissues (P < 0.001). Additionally, high WAVE3 expression was significantly associated with advanced tumor stage (P = 0.008) and positive distant metastasis (P = 0.001). Then, high WAVE3 expression correlated significantly with poor prognosis, and WAVE3 status was identified as an independent significant prognostic factor. Moreover, small interfering RNA targeting WAVE3 was used to inhibit the expression of WAVE3 in HepG2 cells. We found that suppression of WAVE3 could inhibit migration and invasion of HepG2 cells.Conclusion: Our clinical study have characterized WAVE3 as biomarker for HCC progression and metastasis, and more importantly, have identified it as an independent prognostic marker for HCC patients. Our data also indicated that WAVE3 is pivotal in controlling oncogenic phenotypes of human HCC cells. (C) 2014 Published by Elsevier Masson SAS.