Working Paper Article Version 1 This version is not peer-reviewed

5-Hydroxymethylcytosine and Ten-Eleven Translocation Dioxygenases in Head and Neck Carcinoma

Version 1 : Received: 20 July 2019 / Approved: 22 July 2019 / Online: 22 July 2019 (08:55:04 CEST)

How to cite: Misawa, K.; Yamada, S.; Mima, M.; Nakagawa, T.; Kurokawa, T.; Imai, A.; Mochizuki, D.; Oguro, M.; Yamaguchi, Y.; Ishikawa, R.; Endo, S.; Misawa, Y. 5-Hydroxymethylcytosine and Ten-Eleven Translocation Dioxygenases in Head and Neck Carcinoma. Preprints 2019, 2019070237 Misawa, K.; Yamada, S.; Mima, M.; Nakagawa, T.; Kurokawa, T.; Imai, A.; Mochizuki, D.; Oguro, M.; Yamaguchi, Y.; Ishikawa, R.; Endo, S.; Misawa, Y. 5-Hydroxymethylcytosine and Ten-Eleven Translocation Dioxygenases in Head and Neck Carcinoma. Preprints 2019, 2019070237

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.

Subject Areas

5-hmC; ELISA; TET; HNSCC; disease-free survival

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