J Cancer 2019; 10(21):5306-5314. doi:10.7150/jca.34806

Research Paper

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

Kiyoshi Misawa1✉, Satoshi Yamada1, Masato Mima1, Takuya Nakagawa2, Tomoya Kurokawa2, Atsushi Imai1, Daiki Mochizuki1, Kotaro Morita1, Ryuji Ishikawa1, Shiori Endo1, Yuki Misawa1

1. Department of Otolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan
2. Department of Otorhinolaryngology/Head and Neck Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan

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.

Keywords: 5-hmC, ELISA, TET, HNSCC, disease-free survival

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How to cite this article:
Misawa K, Yamada S, Mima M, Nakagawa T, Kurokawa T, Imai A, Mochizuki D, Morita K, Ishikawa R, Endo S, Misawa Y. 5-Hydroxymethylcytosine and ten-eleven translocation dioxygenases in head and neck carcinoma. J Cancer 2019; 10(21):5306-5314. doi:10.7150/jca.34806. Available from http://www.jcancer.org/v10p5306.htm