Genomic screens for genes upregulated by demethylation in colorectal cancer: Possible usefulness for clinical application

Kazuhiko Ogawa, Tohru Utsunomiya, Koshi Mimori, Keishl Yamashita, Masahlro Okamoto, Fumiaki Tanaka, Hiroshi Inoue, Yoichi Ikeda, Motonori Saku, Sadayuki Murayama, Masaki Mori

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11 Citations (Scopus)

Abstract

Inactivation of tumor suppressor genes may result in clinically aggressive tumors and poor prognoses for cancer patients. This study was conducted to investigate the clinical significance of genomic screens for genes up-regulated by demethylation in colorectal cancer. We performed a comprehensive survey of commonly inactivated genes in colorectal cancer through the functional reactivation of epi-genetically silenced genes by 5-Azacytidine. using cDNA microarrays containing 12.814 genes. We then investigated the clinical significance of the identified gene in colorectal cancer patients. Among 41 candidate genes identified by this microarray analysis. 31 (76%) harbored CpG islands, and many of the genes were associated with cancer-test is antigens. Wnt inhibitors, growth factors, and cell cycle regulators. Subsequent analysis by quantitative RT-PCR confirmed the reliability of our microarray strategy. In order to elucidate the potential clinical significance of these identified genes, we selected one of these genes, apolipoprotein D (Apo I)). and investigated its mRNA expression in 63 colorectal cancer patients using quantitative real-time RT-PCR. The mean expression level of Apo D mRNA was significantly lower in cancerous tissues than in non-cancerous tissues (p<0.01), and a lower expression of Apo D was significantly correlated with lymph node metastasis (p<0.05). advanced stages (p<0.05) and poorer overall survival (p<0.05). These results indicated that a genomic screen for genes upregulated by demethylation may be a useful approach for the identification of genes that are of clinical significance in colorectal cancer patients.

Original languageEnglish
Pages (from-to)417-426
Number of pages10
JournalInternational journal of oncology
Volume27
Issue number2
Publication statusPublished - Aug 1 2005

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Ogawa, K., Utsunomiya, T., Mimori, K., Yamashita, K., Okamoto, M., Tanaka, F., Inoue, H., Ikeda, Y., Saku, M., Murayama, S., & Mori, M. (2005). Genomic screens for genes upregulated by demethylation in colorectal cancer: Possible usefulness for clinical application. International journal of oncology, 27(2), 417-426.