title: Prognostic value of aberrant promoter hypermethylation of tumor-related genes in early-stage head and neck cancer.
abstract: Staging and pathological grading are useful, but imperfect predictors of recurrence in head and neck squamous cell carcinoma (HNSCC). Accordingly, molecular biomarkers that predict the risk of recurrence are necessary to improve clinical outcomes. The methylation statuses of the promoters of 11 tumor-related genes (p16, RASSF1A, E-cadherin, H-cadherin, MGMT, DAPK, DCC, COL1A2, TAC1, SST, and GALR1) were analyzed in 133 HNSCC cases using quantitative methylation-specific PCR. We detected frequent methylation of p16 (44%), RASSF1A (18%), E-cadherin (53%), H-cadherin (35%), MGMT (35%), DAPK (53%), DCC (42%), COL1A2 (44%), TAC1 (61%), SST (64%), and GALR1 (44%) in HNSCC. Disease-free survival was lower in patients with 6-11 methylated genes than in those with 0-5 methylated genes (log-rank test, P = 0.001). In a multivariate Cox proportional hazards analysis, the methylation of E-cadherin, COL1A2, TAC1, and GALR1 was associated with poor survival, with hazard ratios of 4.474 (95% CI, 1.241-16.124). In a joint analysis of these four genes, patients with 2-4 methylated genes had a significantly lower survival rate than those with 0-1 methylated genes in early-stage HNSCC. Importantly, the methylation of some genes was closely related to poor prognosis in early-stage HNSCC, providing strong evidence that these hypermethylated genes are valuable biomarkers for prognostic evaluation.
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Misawa
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Mochizuki
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Imai
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan.
authors.forename: Shiori
authors.initials: S
authors.lastname: Endo
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Mima
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Misawa
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, Jichi Medical University, Tochigi, Japan.
authors.forename: Takeharu
authors.initials: T
authors.lastname: Kanazawa
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, Laboratory of Head and Neck Cancer Biology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Carey
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mineta
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D024042:Collagen Type I / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; 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*; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C000601279:COL1A2 protein, human; D024042:Collagen Type I; D044091:Receptor, Galanin, Type 1
keywords: biomarker; head and neck cancer; hypermethylation; metastases; tumor-suppressor genes