Site-specific methylation patterns of the GAL and GALR1/2 genes in head and neck cancer: Potential utility as biomarkers for prognosis.
The aim of this study was to evaluate the prognostic value of the promoter methylation status of galanin (GAL) and galanin receptor 1/2 (GALR1/2) by assessing their association with disease-free survival and known prognostic factors in head and neck cancer. We generated methylation profiles of GAL and GALR1/2 in tumor samples obtained from 202 patients with head and neck squamous cell carcinoma (HNSCC); these included 43 hypopharynx, 42 larynx, 59 oral cavity, and 58 oropharynx tumor samples. CpG island hypermethylation status of the three genes was analyzed using quantitative methylation-specific PCR (Q-MSP). In order to determine the prognostic value of the methylation status of these genes, the associations between methylation index and various clinical characteristics, especially tumor site, were assessed for tumors from patients with HNSCC. The methylation index was positively correlated with female gender (P = 0.008) and disease recurrence (P = 0.01) in oral cancer and human papillomavirus (HPV)-positive (P = 0.004) status and disease recurrence (P = 0.005) in oropharyngeal cancer. Among patients with oral and oropharyngeal cancer, promoter hypermethylation of GAL, GALR1, or GALR2 was statistically correlated with a decrease in disease-free survival (log-rank test, P = 0.036 and P = 0.042, respectively). Furthermore, methylation of GAL, GALR1, or GALR2 exhibited the highest association with poor survival (log-rank test, P = 0.018) in patients with HPV-negative oropharyngeal cancers. As such, GAL and GALR1/2 methylation status may serve as an important site-specific biomarker for prediction of clinical outcome in patients with HNSCC. © 2016 Wiley Periodicals, Inc.
Department of Otolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan.
Kiyoshi
K
Misawa
Department of Otolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan.
Daiki
D
Mochizuki
Department of Otolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan.
Shiori
S
Endo
Department of Otolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan.
Masato
M
Mima
Department of Otolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan.
Yuki
Y
Misawa
Department of Otolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan.
Atsushi
A
Imai
Department of Tumour Pathology, Hamamatsu University School of Medicine, Shizuoka, Japan.
Kazuya
K
Shinmura
Department of Otolaryngology/Head and Neck Surgery, Jichi Medical University, Tochigi, Japan.
Takeharu
T
Kanazawa
Laboratory of Head and Neck Cancer Biology, Department of Otolaryngology/Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan.
Thomas E
TE
Carey
Department of Otolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan.
Hiroyuki
H
Mineta
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D019004:Galanin / Q000235:genetics*; D056726:Genetic Association Studies; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011401:Promoter Regions, Genetic; D044091:Receptor, Galanin, Type 1 / Q000235:genetics*; D044092:Receptor, Galanin, Type 2 / Q000235:genetics*; D000077195:Squamous Cell Carcinoma of Head and Neck; D016019:Survival Analysis
D014408:Biomarkers, Tumor; C056567:GAL protein, human; D044091:Receptor, Galanin, Type 1; D044092:Receptor, Galanin, Type 2; D019004:Galanin
GALR1/2; HPV; galanin; hypermethylation; oral and oropharyngeal cancer