5-Hydroxymethylcytosine and ten-eleven translocation dioxygenases in head and neck carcinoma.

Abstract

Ten-eleven translocation (TET) enzymes are implicated in DNA demethylation through dioxygenase activity, which converts 5-methylcytosine to 5-hydroxymethylcytosine (5-hmC). However, the specific roles of TET enzymes and 5-hmC levels in head and neck squamous cell carcinoma (HNSCC) have not yet been evaluated. In this study, we analyzed 5-hmC levels and TET mRNA expression in a well-characterized dataset of 117 matched pairs of HNSCC tissues and normal tissues. 5-hmC levels and TET mRNA expression were examined via enzyme-linked immunosorbent assay and quantitative real-time PCR, respectively. 5-hmC levels were evaluated according to various clinical characteristics and prognostic implications. Notably, we found that 5-hmC levels were significantly correlated with tumor stage (P = 0.032) and recurrence (P = 0.018). Univariate analysis revealed that low levels of 5-hmC were correlated with poor disease-free survival (DFS; log-rank test, P = 0.038). The expression of TET family genes was not associated with outcomes. In multivariate analysis, low levels of 5-hmC were evaluated as a significant independent prognostic factor of DFS (hazard ratio: 2.352, 95% confidence interval: 1.136-4.896; P = 0.021). Taken together, our findings showed that reduction of TET family gene expression and subsequent low levels of 5-hmC may affect the development of HNSCC.

• Authors: Kiyoshi Misawa, Satoshi Yamada, Masato Mima, Takuya Nakagawa, Tomoya Kurokawa, Atsushi Imai, Daiki Mochizuki, Kotaro Morita, Ryuji Ishikawa, Shiori Endo, Yuki Misawa
• Journal: Journal of Cancer (J Cancer) Vol. 10 Issue 21 Pg. 5306-5314 ( 2019) ISSN: 1837-9664 [Print] Australia
• PMID: 31602281 (Publication Type: Journal Article)
• Copyright: © The author(s).