Prognostic Significance of Promoter DNA Hypermethylation of cysteine dioxygenase 1 (CDO1) Gene in Primary Breast Cancer

Naoko Minatani, Mina Waraya, Keishi Yamashita, Mariko Kikuchi, Hideki Ushiku, Ken Kojo, Akira Ema, Hiroshi Nishimiya, Yoshimasa Kosaka, Hiroshi Katoh, Norihiko Sengoku, Hirokazu Tanino, David Sidransky, Masahiko Watanabe

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Abstract

Using pharmacological unmasking microarray, we identified promoter DNA methylation of cysteine dioxygenase 1 (CDO1) gene in human cancer. In this study, we assessed the clinicopathological significance of CDO1 methylation in primary breast cancer (BC) with no prior chemotherapy. The CDO1 DNA methylation was quantified by TaqMan methylation specific PCR (Q-MSP) in 7 BC cell lines and 172 primary BC patients with no prior chemotherapy. Promoter DNA of the CDO1 gene was hypermethylated in 6 BC cell lines except SK-BR3, and CDO1 gene expression was all silenced at mRNA level in the 7 BC cell lines. Quantification of CDO1 methylation was developed using Q-MSP, and assessed in primary BC. Among the clinicopathologic factors, CDO1 methylation level was not statistically significantly associated with any prognostic factors. The log-rank plot analysis elucidated that the higher methylation the tumors harbored, the poorer prognosis the patients exhibited. Using the median value of 58.0 as a cut-off one, disease specific survival in BC patients with CDO1 hypermethylation showed significantly poorer prognosis than those with hypomethylation (p = 0.004). Multivariate Cox proportional hazards model identified that CDO1 hypermethylation was prognostic factor as well as Ki-67 and hormone receptor status. The most intriguingly, CDO1 hypermethylation was of robust prognostic relevance in triple negative BC (p = 0.007). Promoter DNA methylation of CDO1 gene was robust prognostic indicator in primary BC patients with no prior chemotherapy. Prognostic relevance of the CDO1 promoter DNA methylation is worthy of being paid attention in triple negative BC cancer.

Original languageEnglish (US)
Article numbere0144862
JournalPloS one
Volume11
Issue number1
DOIs
StatePublished - Jan 1 2016

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Minatani, N., Waraya, M., Yamashita, K., Kikuchi, M., Ushiku, H., Kojo, K., Ema, A., Nishimiya, H., Kosaka, Y., Katoh, H., Sengoku, N., Tanino, H., Sidransky, D., & Watanabe, M. (2016). Prognostic Significance of Promoter DNA Hypermethylation of cysteine dioxygenase 1 (CDO1) Gene in Primary Breast Cancer. PloS one, 11(1), [e0144862]. https://doi.org/10.1371/journal.pone.0144862