Yang Lian-Yue, Tao Yi-Ming, Ou Di-Peng, Wang Wei, Chang Zhi-Gang, Wu Fan
Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, People's Republic of China.
Clin Cancer Res. 2006 Oct 1;12(19):5673-9. doi: 10.1158/1078-0432.CCR-06-0022.
Because of its role in cell migration, the Wiskott-Aldrich syndrome protein family verprolin-homologous protein (WAVE) 2 has been implicated in cancer metastasis. Evidence to support such a role of WAVE2 in human cancer, however, is lacking. We thus examined the expression of WAVE2 in hepatocellular carcinoma (HCC) tissues to test whether the levels of WAVE2 expression correlated to the progression of HCC.
Samples of 112 HCC patients were determined immunohistochemically for WAVE2 expression and the correlation of WAVE2 levels with prognosis was analyzed. Among the 112 cases, 31 paired HCC and paracarcinomatous liver tissue specimens were analyzed for WAVE2 levels by reverse transcription-PCR and Western blotting, respectively.
Among 112 cases of HCCs, the immunohistochemistry data indicated significant increase of WAVE2 expression levels in 71 cases. Importantly, the increased WAVE2 expression correlated with the multiple tumor nodules (P = 0.008), the absence of capsular formation (P = 0.035), Edmondson-Steiner grade (P = 0.009), vein invasion (P = 0.023), and a shortened median survival time (326 versus 512 days; P = 0.003). Multivariable Cox regression analysis revealed the WAVE2 expression level was an independent factor for prognosis. The immunohistochemistry data were further confirmed by results of reverse transcription-PCR and Western analysis of 31 HCC cases, in which the WAVE2 mRNA and protein in HCC tissues were significantly elevated when compared with paracarcinomatous liver tissue (P < 0.001).
WAVE2 expression is elevated in HCC tissues, which correlates with a poor prognosis, suggesting WAVE2 as a candidate prognostic marker of HCC.
威斯科特-奥尔德里奇综合征蛋白家族维普洛林同源蛋白（WAVE）2因在细胞迁移中发挥作用，而与癌症转移有关。然而，缺乏支持WAVE2在人类癌症中发挥这种作用的证据。因此，我们检测了肝细胞癌（HCC）组织中WAVE2的表达，以测试WAVE2表达水平是否与HCC的进展相关。
对112例HCC患者的样本进行免疫组织化学检测以确定WAVE2的表达，并分析WAVE2水平与预后的相关性。在这112例病例中，分别通过逆转录聚合酶链反应（RT-PCR）和蛋白质印迹法对31对HCC及癌旁肝组织标本进行WAVE2水平分析。
在112例HCC病例中，免疫组织化学数据显示71例WAVE2表达水平显著升高。重要的是，WAVE2表达增加与多个肿瘤结节（P = 0.008）、无包膜形成（P = 0.035）、埃德蒙森-斯坦纳分级（P = 0.009）、静脉侵犯（P = 0.023）以及中位生存时间缩短（326天对512天；P = 0.003）相关。多变量Cox回归分析显示WAVE2表达水平是预后的独立因素。31例HCC病例的RT-PCR和蛋白质印迹分析结果进一步证实了免疫组织化学数据，其中HCC组织中的WAVE2信使核糖核酸（mRNA）和蛋白质与癌旁肝组织相比显著升高（P < 0.001）。
HCC组织中WAVE2表达升高，这与预后不良相关，提示WAVE2作为HCC的候选预后标志物。
