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

2017; Impact Journals LLC; Volume: 8; Issue: 44 Linguagem: Inglês

10.18632/oncotarget.19356

1949-2553

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

Hedgehog Signaling Pathway Studies

// Kiyoshi Misawa 1 , Atsushi Imai 1 , Daiki Mochizuki 1 , Yuki Misawa 1 , Shiori Endo 1 , Seiji Hosokawa 1 , Ryuji Ishikawa 1 , Masato Mima 1 , Kazuya Shinmura 2 , Takeharu Kanazawa 3 and Hiroyuki Mineta 1 1 Department of Otolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan 2 Department of Tumour Pathology, Hamamatsu University School of Medicine, Shizuoka, Japan 3 Department of Otolaryngology/Head and Neck Surgery, Jichi Medical University, Tochigi, Japan Correspondence to: Kiyoshi Misawa, email: kiyoshim@hama-med.ac.jp Keywords: neuropeptide receptors, GPCR, head and neck cancer, epigenetic markers, metastases Received: March 15, 2017     Accepted: June 29, 2017     Published: July 18, 2017 ABSTRACT Staging and pathological grading systems are useful but imperfect predictors of recurrence in head and neck squamous cell carcinoma (HNSCC). To identify potential prognostic markers, we examined the methylation status of eight neuropeptide receptor gene promoters in 231 head and neck squamous cell carcinomas. The NPFFR1 , NPFFR2 , HCRTR1 , HCRTR2 , NPY1R , NPY2R , NPY4R , and NPY5R promoters were methylated in 80.5%, 79.2%, 67.1%, 73.2%, 35.1%, 36.4%, 38.5%, and 35.9% of the samples, respectively. In a multivariate Cox proportional hazards analysis, the odds ratio for recurrence was 2.044 (95% confidence interval [CI], 1.323–3.156; P = 0.001) when the NPY2R promoter was methylated. In patients without lymph node metastasis (n = 100), methylation of NPY2R (compared with methylation of the other seven genes) best correlated with poor disease-free survival (DFS) (odds ratio, 2.492; 95% CI, 1.190–5.215; P = 0.015). In patients with oral cancer (n = 69), methylated NPY1R and NPY2R were independent prognostic factors for poor DFS, both individually and, even more so, in combination (odds ratio, 3.90; 95% CI, 1.523–9.991; P = 0.005). Similar findings were observed for NPY2R and NPY4R in patients with oropharyngeal cancer (n = 162) (odds ratio, 5.663; 95% CI, 1.507–21.28; P = 0.010).