Lau S H, Sham J S T, Xie D, Tzang C-H, Tang D, Ma N, Hu L, Wang Y, Wen J-M, Xiao G, Zhang W-M, Lau G K K, Yang M, Guan X-Y
Department of Clinical Oncology, The University of Hong Kong, Pokfulam, Hong Kong, China.
Oncogene. 2006 Feb 23;25(8):1242-50. doi: 10.1038/sj.onc.1209141.
To identify genes associated with tumor metastasis in hepatocellular carcinoma (HCC), gene expression profiles between a pair of primary HCC (H2-P) and their matched metastatic HCC (H2-M) were compared. Overexpression of clusterin (CLU) was found in H2-M cells. To determine the roles CLU played in HCC metastasis, CLU was transfected into H2-P cells. Overexpression of CLU in H2-P cells increased cell migration by twofold in vitro and formation of metastatic tumor nodules in liver by eightfold in vivo. To evaluate the correlation of CLU expression with HCC metastasis, the expression levels of CLU in HCCs were investigated using a tissue microarray (TMA) containing 104 pairs of primary HCCs and their matched metastases. The frequency of CLU overexpression increased significantly in metastatic HCCs (59.1%) compared with that in primary tumors (32.6%, P<0.001). To gain additional insight into the function of CLU, the expression profile of H2P-CLU was compared with vector-transfected H2-P cells by cDNA microarray. A total of 35 upregulated and 14 downregulated genes were detected in H2P-CLU. One of the upregulated genes known as YKL-40, which is implicated in matrix-remodeling and metastasis, was further studied using TMA. A significant correlation (P<0.001) between the expression levels of YKL-40 and CLU was observed, implying that the CLU-YKL-40 pathway may play an important role in HCC metastasis.
为了鉴定与肝细胞癌（HCC）肿瘤转移相关的基因，比较了一对原发性HCC（H2-P）及其匹配的转移性HCC（H2-M）之间的基因表达谱。在H2-M细胞中发现了簇集蛋白（CLU）的过表达。为了确定CLU在HCC转移中所起的作用，将CLU转染到H2-P细胞中。H2-P细胞中CLU的过表达在体外使细胞迁移增加了两倍，在体内使肝内转移瘤结节的形成增加了八倍。为了评估CLU表达与HCC转移的相关性，使用包含104对原发性HCC及其匹配转移灶的组织微阵列（TMA）研究了HCC中CLU的表达水平。与原发性肿瘤（32.6%，P<0.001）相比，转移性HCC中CLU过表达的频率显著增加（59.1%）。为了进一步深入了解CLU的功能，通过cDNA微阵列比较了H2P-CLU与载体转染的H2-P细胞的表达谱。在H2P-CLU中总共检测到35个上调基因和14个下调基因。其中一个上调基因称为YKL-40，它与基质重塑和转移有关，使用TMA对其进行了进一步研究。观察到YKL-40和CLU的表达水平之间存在显著相关性（P<0.001），这意味着CLU-YKL-40通路可能在HCC转移中起重要作用。
