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Association of TET3 epigenetic inactivation with head and neck cancer.

ABSTRACT: The aim of this study was to clarify the epigenetic regulation of ten eleven translocation protein (TET) family genes, which can provide insights into the mechanisms of tumorigenesis and the risk of disease recurrence in head and neck squamous cell carcinoma (HNSCC). We generated methylation profiles of TET1, TET2 and TET3 genes in tumor samples obtained from 233 patients with HNSCC; these included 57 hypopharynx, 44 larynx, 69 oral cavity, and 63 oropharynx tumor samples. The mRNA expression and promoter DNA methylation of TET family genes were examined via quantitative RT-PCR and methylation-specific PCR, respectively. Promoter methylation was compared with various clinical characteristics and the TET methylation index (TE-MI). The TE-MI, representing the number of methylation events in TET family genes, was positively correlated with alcohol consumption (P = 0.004), high-risk human papilloma virus (HPV) status (P = 0.004) and disease recurrence (P = 0.002). The simultaneous methylation analysis of TET family genes was correlated with reduced disease-free survival in unfavorable event groups (log-rank test, P = 0.026). In the multivariate Cox proportional hazards analysis, TET3 methylation in T1 and T2 tumor stages, oropharyngeal cancer, and oral cancer patients exhibited high association with poor survival (hazard ratio: 2.64, P = 0.014; 3.55, P = 0.048; 2.63, P = 0.028, respectively). A joint analysis of the tumor suppressor gene methylation index showed a significant trend toward a higher TE-MI. The methylation status of TET3 was independently associated with aggressive tumor behavior and a global effect on DNA methylation status in HNSCC.

SUBMITTER: Misawa K

PROVIDER: S-EPMC5966249 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Association of TET3 epigenetic inactivation with head and neck cancer.

Misawa Kiyoshi K Imai Atsushi A Mochizuki Daiki D Mima Masato M Endo Shiori S Misawa Yuki Y Kanazawa Takeharu T Mineta Hiroyuki H

Oncotarget 20180511 36

The aim of this study was to clarify the epigenetic regulation of ten eleven translocation protein (TET) family genes, which can provide insights into the mechanisms of tumorigenesis and the risk of disease recurrence in head and neck squamous cell carcinoma (HNSCC). We generated methylation profiles of TET1, TET2 and TET3 genes in tumor samples obtained from 233 patients with HNSCC; these included 57 hypopharynx, 44 larynx, 69 oral cavity, and 63 oropharynx tumor samples. T ...[more]

PMID: 29849955

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Project description:BACKGROUND:Chronic inflammation is a risk factor for head and neck squamous cell carcinoma (HNSCC) and other diseases. Prostanoid receptors are clearly involved in the development of many types of cancer. However, their role is not simple and is poorly understood in HNSCC. METHODS:Methylation profiles of prostanoid receptor family genes were generated for tumour samples obtained from 274 patients with HNSCC, including 69 hypopharynx, 51 larynx, 79 oral cavity, and 75 oropharynx tumour samples, by quantitative methylation-specific PCR. Promoter methylation was then evaluated with respect to various clinical characteristics and patient survival. RESULTS:The mean number of methylated genes per sample was 2.05?±?2.59 (range 0 to 9). Promoters of PTGDR1, PTGDR2, PTGER1, PTGER2, PTGER3, PTGER4, PTGFR, PTGIR, and TBXA2R were methylated in 43.8%, 18.2%, 25.5%, 17.5%, 41.2%, 8.0%, 19.3%, 20.4%, and 11.3% of the samples, respectively. Methylation indices for prostanoid receptor family genes tended to be higher as the number of TET methylation events increased. Patients with 5-9 methylated genes had a significantly lower survival rate than that of patients with 0-4 methylated genes (log-rank test, P=?0.007). In multivariate analyses, PTGDR1 methylation was most highly correlated with recurrence in patients with hypopharyngeal cancer (P?=?0.014). A similar correlation was observed for PTGER4 in patients with laryngeal cancer (P?=?0.046). Methylation of the PTGIR and TBXA2R promoters was positively correlated with recurrence in oropharyngeal cancer (P?=?0.028 and P?=?0.006, respectively). Moreover, Patients with 5-9 methylated genes were extremely lower of 5hmC levels (P?=?0.035) and was correlated with increasing expression of DNMT3A and DNMT3B (P?<?0.05 and P?<?0.05, respectively). CONCLUSION:We characterised the relationship between the methylation status of prostanoid receptor genes and recurrence in HNSCC. These results provide new perspectives for the development of molecular targeted treatment approaches.

Dataset Information

Association of TET3 epigenetic inactivation with head and neck cancer.

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Association of TET3 epigenetic inactivation with head and neck cancer.

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