Dong Hyuk Ki^1,2,3, Hei-Cheul Jeung^1,2, Chan Hee Park^1,2,4, Seung Hee Kang^1,2, Gui Youn Lee^1,2,3, Won Suk Lee^1,2,4, Nam Kyu Kim⁵, Hyun Chul hung^1,2,3,4,6 and Sun Young Rha<sup>1,2,4,6,*

1</sup> Division of Genomics and Translational Research, Cancer Metastasis Research Center, Yonsei University College of Medicine, Seoul, Korea
² Division of Tumor Biology, Yonsei Cancer Center, Yonsei Cancer Research Institute, Yonsei University College of Medicine, Seoul, Korea
³ Division of Transcriptomics, National Biochip Research Center, Yonsei University College of Medicine, Seoul, Korea
⁴ Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
⁵ Department of General Surgery, Yonsei University College of Medicine, Seoul, Korea
⁶ Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea

^*Corresponding author

Abstract
Liver metastasis is one of the major causes of death in colorectal cancer (CRC) patients. To understand this process, we investigated whether the gene expression profiling of matched colorectal carcinomas and liver metastases could reveal key molecular events involved in tumor progression and metastasis. We performed experiments using a cDNA microarray containing 17,104 genes with the following tissue samples: paired tissues of 25 normal colorectal mucosa, 27 primary colorectal tumors, 13 normal liver and 27 liver metastasis, and 20 primary colorectal tumors without liver metastasis. To remove the effect of normal cell contamination, we selected 4,583 organ-specific genes with a false discovery rate (FDR) of 0.0067% by comparing normal colon and liver tissues using significant analysis of microarray, and these genes were excluded from further analysis. We then identified and validated 46 liver metastasis-specific genes with an accuracy of 83.3% by comparing the expression of paired primary colorectal tumors and liver metastases using prediction analysis of microarray. The 46 selected genes contained several known oncogenes and 2 ESTs. To confirm that the results correlated with the microarray expression patterns, we performed RT-PCR with WNT5A and carbonic anhydrase II. Additionally, we observed that 21 of the 46 genes were differentially expressed (FDR = 2.27%) in primary tumors with synchronous liver metastasis compared with primary tumors without liver metastasis. We scanned the human genome using a cDNA microarray and identified 46 genes that may play an important role in the progression of liver metastasis in CRC. ⓒ 2007 Wiley-Liss, Inc.

Keywords : colorectal cancer; liver metastasis; gene expression profiling; cDNA microarray