Genes encoding neuropeptide receptors are epigenetic markers in patients with head and neck cancer: a site-specific analysis

Misawa, Kiyoshi; Imai, Atsushi; Mochizuki, Daiki; Misawa, Yuki; Endo, Shiori; Hosokawa, Seiji; Ishikawa, Ryuji; Mima, Masato; Shinmura, Kazuya; Kanazawa, Takemichi; Mineta, Hiroyuki

doi:10.18632/oncotarget.19356

Cited by 19 publications

(14 citation statements)

References 39 publications

(40 reference statements)

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“…Extraction and bisulfite conversion of genomic DNA from 233 primary HNSCC and 36 noncancerous mucosal samples were performed using the MethylEasy Xceed Rapid DNA Bisulfite Modification Kit (Takara) per manufacturer instructions [ 37 ]. The CpG island methylation levels in the promoters of the TET1, TET2, and TET3 genes were determined via Q-MSP with the Takara Thermal Cycler Dice Real Time System TP800 (Takara); the primer sets are listed in Supplementary Table 2 .…”

Section: Methodsmentioning

confidence: 99%

Association of TET3 epigenetic inactivation with head and neck cancer

et al. 2018

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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.

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Section: Methodsmentioning

confidence: 99%

Association of TET3 epigenetic inactivation with head and neck cancer

et al. 2018

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“…G protein-coupled receptors (GPCRs) are the largest class of cell-surface receptors and are involved in many cancers, including head and neck squamous cell carcinoma (HNSCC) [5,6]. GPCRs are modulated by a variety of endogenous and synthetic ligands and are major drug targets [7].…”

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Prostanoid receptor genes confer poor prognosis in head and neck squamous cell carcinoma via epigenetic inactivation

et al. 2020

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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,

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“…The normalized methylation value (NMV) was determined as follows: NMV = (Target gene-S/Target gene-FM)/(ACTB-S/ACTB-FM), where Target gene-S and Target gene-FM represent the target gene methylation levels in the tumor sample and universal methylated DNA control, respectively, and ACTB-S and ACTB-FM represent the ACTB (which encodes β-actin) methylation levels in the sample and control, respectively. Analysis was performed using the software (version 1.03A) for the Thermal Cycler Dice Real Time System TP800 (TaKaRa), according to the manufacturer’s directions [ 13 ].…”

Section: Methodsmentioning

confidence: 99%

“…The overall methylation rates in the individual samples were determined by calculating the methylation index (MI). MI was defined as the ratio of the number of methylated genes to the number of tested genes in each sample [ 13 ].…”

Section: Methodsmentioning

confidence: 99%

The neuropeptide genes SST, TAC1, HCRT, NPY, and GAL are powerful epigenetic biomarkers in head and neck cancer: a site-specific analysis

et al. 2018

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BackgroundStaging and pathological grading systems are convenient but imperfect predictors of recurrence in head and neck squamous cell carcinoma (HNSCC). Identifying biomarkers for HNSCC that will progress and cause death is a critical research area, particularly if the biomarker can be linked to selection of patients. Therefore, to identify potential alternative prognostic markers, we investigated the methylation status of five neuropeptide gene promoters. The promoter methylation status was determined by quantitative methylation-specific PCR in 230 cases of HNSCC; 58 hypopharynx, 45 larynx, 56 oropharynx, and 71 oral cavity tumor samples were studied.ResultsThe somatostatin (SST), tachykinin precursor 1 (TAC1), hypocretin neuropeptide precursor (HCRT), neuropeptide Y (NPY), and galanin (GAL) promoters were methylated in 84.3, 63.5, 32.6, 28.3, and 20.0%, respectively, of the samples. The mean number of methylated genes per sample was 2.29 (range, 0–5). Disease-free survival was lower in patients with 3–5 methylated genes than in those with 0–2 methylated genes (log-rank test, P = 0.007). In multivariate Cox proportional hazards analysis, TAC1 and GAL promoter methylation independently predicted recurrence (odds ratios 1.620, 95% confidence interval [CI] 1.018–2.578, P = 0.042, and odds ratios 1.692, 95% CI 1.063–2.694, P = 0.027, respectively). In patients with oral cancer, TAC1 methylation showed the best correlation with poor survival (odds ratio 4.427, 95% CI 1.634–12.00, P = 0.003). Similar findings were observed for HCRT and GAL in patients with laryngeal cancer and oropharyngeal cancer, respectively.ConclusionIn this study, we demonstrated the methylation status of the neuropeptide-encoding genes SST, TAC1, HCRT, NPY, and GAL and its relationship with recurrence and survival in HNSCC. These methylation changes may serve as potential molecular markers for defining the risk and prognosis of HNSCC.Electronic supplementary materialThe online version of this article (10.1186/s13148-018-0485-0) contains supplementary material, which is available to authorized users.

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Genes encoding neuropeptide receptors are epigenetic markers in patients with head and neck cancer: a site-specific analysis

Cited by 19 publications

References 39 publications

Association of TET3 epigenetic inactivation with head and neck cancer

Association of TET3 epigenetic inactivation with head and neck cancer

Prostanoid receptor genes confer poor prognosis in head and neck squamous cell carcinoma via epigenetic inactivation

The neuropeptide genes SST, TAC1, HCRT, NPY, and GAL are powerful epigenetic biomarkers in head and neck cancer: a site-specific analysis

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