Whole genome analysis for liver metastasis gene signatures in colorectal cancer

Hyuk Ki Dong, Hei Cheul Jeung, Hee Park Chan, Hee Kang Seung, Youn Lee Gui, Suk Lee Won, Kyu Kim Nam, Chul Chung Hyun, Young Rha Sun

Research output: Contribution to journalArticle

159 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2005-2012
Number of pages8
JournalInternational Journal of Cancer
Volume121
Issue number9
DOIs
Publication statusPublished - 2007 Nov 1

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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