Brief Articles
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World J Gastroenterol. Jan 21, 2009; 15(3): 356-365
Published online Jan 21, 2009. doi: 10.3748/wjg.15.356
Genomic-wide analysis of lymphatic metastasis-associated genes in human hepatocellular carcinoma
Chun-Feng Lee, Zhi-Qiang Ling, Ting Zhao, Shih-Hua Fang, Weng-Cheng Chang, San-Chih Lee, Kuan-Rong Lee
Chun-Feng Lee, Kuan-Rong Lee, Institute of Molecular Medicine, National Tsing Hua University, 101, Section 2, Kuang-Fu Road, Hsinchu, Taiwan 300, China
Zhi-Qiang Ling, Zhejiang Academy of Medical Sciences, 182 Tianmushan Road, Hangzhou 310013, Zhejiang Province, China
Ting Zhao, Department of Surgery, Zhejiang Provincial People Hospital, 158, Shangtang Road, Hangzhou 310014, Zhejiang Province, China
Shih-Hua Fang, Institute of Athletics, National Taiwan Sport University, 16, Sec. 1, Shuang-Shih Road, Taichung City, Taiwan 404, China
Weng-Cheng Chang, Graduate Institute of Medical Sciences, Chang Jung Christian University, 396, Chang Jung Road, Sec. 1, Kway Jen, Taiwan 711, China
San-Chih Lee, Department of Nursing, Shu-Zen College of Medicine and Management, 452, Huanciou Road, Lujhu Township, Kaohsiung County, Taiwan 821, China
Author contributions: Lee CF performed most of the experiments, participated in most of the data analysis and drafted the manuscript; Lee KR and Lee SC were the leaders of this project, who conceived the study, designed the research route, guided the experiments and the data analysis, and suggested revisions of the manuscript; Ling ZQ carried out cDNA microarray, real-time RT-PCR experiments and provided critical comments and suggested revisions of the manuscript; Fang SH and Chang WC provided the technique and opinions for this study and also suggested the revisions of the manuscript; Zhao T carried out the hepatocellular carcinoma samples collection and preparation, and participated in parts of experiments. All authors read and approved the final manuscript.
Correspondence to: Kuan-Rong Lee, Institute of Molecular Medicine, National Tsing Hua University, 101, Section 2, Kuang-Fu Road, Hsinchu, Taiwan 300, China. krlee@mx.nthu.edu.tw
Telephone: +86-3-5742755
Fax: +86-3-5715934
Received: October 13, 2008
Revised: December 12, 2008
Accepted: December 19, 2008
Published online: January 21, 2009
Abstract

AIM: To identify the genes related to lymph node metastasis in human hepatocellular carcinoma (HCC), 32 HCC patients with or without lymph node metastasis were investigated by high-throughput microarray comprising 886 genes.

METHODS: The samples of cancerous and non-cancerous paired tissue were taken from 32 patients with HCC who underwent hepatectomy with lymph node dissection. Total RNA was extracted from the cells obtained by means of laser microdissection (LCM) and was amplified by the T7-based amplification system. Then, the amplified samples were applied in the cDNA microarray comprising of 886 genes.

RESULTS: The results demonstrated that 25 up-regulated genes such as cell membrane receptor, intracellular signaling and cell adhesion related genes, and 48 down-regulated genes such as intracellular signaling and cell cycle regulator-related genes, were correlated with lymph node metastasis in HCC. Amongst them were included some interesting genes, such as MET, EPHA2, CCND1, MMP2, MMP13, CASP3, CDH1, and PTPN2. Expression of 16 genes (MET, CCND1, CCND2, VEGF, KRT18, RFC4, BIRC5, CDC6, MMP2, BCL2A1, CDH1, VIM, PDGFRA, PTPN2, SLC25A5 and DSP) were further confirmed by real-time quantitative reverse transcriptional polymerase chain reaction (RT-PCR).

CONCLUSION: Tumor metastasis is an important biological characteristic, which involves multiple genetic changes and cumulation. This genome-wide information contributes to an improved understanding of molecular alterations during lymph node metastasis in HCC. It may help clinicians to predict metastasis of lymph nodes and assist researchers in identifying novel therapeutic targets for metastatic HCC patients.

Keywords: Hepatocellular carcinoma; Lymphatic metastasis-associated genes; cDNA microarray; Expression profiling