J Cancer 2019; 10(21):5306-5314. doi:10.7150/jca.34806
5-Hydroxymethylcytosine and ten-eleven translocation dioxygenases in head and neck carcinoma
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
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
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