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).
Highlights
Kiyoshi Misawa1, Atsushi Imai1, Daiki Mochizuki1, Yuki Misawa1, Shiori Endo1, Seiji Hosokawa1, Ryuji Ishikawa1, Masato Mima1, Kazuya Shinmura2, Takeharu
The odds ratio was significantly higher in patients with no lymph node metastasis (n = 100) in whom the NPY2R promoter was methylated versus unmethylated (Table 3)
Status, smoking status, alcohol intake, tumor stage, and gene methylation status all indicated the likelihood of recurrence in patients with methylated NPY1R and NPY2R
Summary
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. In a multivariate Cox proportional hazards analysis, the odds ratio for recurrence was 2.044 Improvement of patient care requires molecular classification of head and neck squamous cell carcinomas (HNSCCs) that provides both prognostic and mechanistic information
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