1. ¹Department of Clinical Oncology, The University of Hong Kong, Pokfulam, Hong Kong, China
2. ²State Key Laboratory of Oncology in Southern China, Cancer Center, Guangzhou, China
3. ³Department of Biology and Chemistry, The City University of Hong Kong, Hong Kong, China
4. ⁴Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
5. ⁵Department of Pathology, Sun Yat-sen University, Guangzhou, China
6. ⁶Department of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China

Correspondence: Dr X-Y Guan, Department of Clinical Oncology, The University of Hong Kong, Room 109, Estate Building, 10 Sassoon Road, Pokfulam, Hong Kong, China. E-mail: xyguan@hkucc.hku.hk

Received 28 June 2005; Revised 10 August 2005; Accepted 25 August 2005; Published online 17 October 2005.

Abstract

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.