title: Frequent promoter hypermethylation of tachykinin-1 and tachykinin receptor type 1 is a potential biomarker for head and neck cancer.
abstract: OBJECTIVE
  The aim of this study was to define TAC1 and TACR1 methylation profiles for head and neck squamous cell carcinoma (HNSCC) tumors at diagnosis and follow-up and to evaluate their prognostic significance and value as a biomarker of recurrence.
  
  
  METHODS
  TAC1 and TACR1 expression was measured in a panel of cell lines by quantitative RT-PCR. The TAC1 and TACR1 promoter methylation status was determined by quantitative methylation-specific PCR.
  
  
  RESULTS
  Methylation was associated with TAC1 and TACR1 transcription inhibition. TAC1 methylation in 49/100 (49 %) of HNSCC tumor specimens significantly correlated with p16 methylation (P = 0.010), E-cadherin methylation (P = 0.041), galanin methylation (P = 0.037), and disease-free survival (P = 0.002). Stage III and IV patients manifesting TAC1 hypermethylation had significantly shorter survivals than did patients without TAC1 methylation (P = 0.022). TACR1 methylation in 34/100 (34 %) cases was significantly correlated with galanin methylation (P = 0.014) and GALR1 methylation (P = 0.004). TAC1 promoter hypermethylation was statistically correlated with reduced disease-free survival (log-rank test, P = 0.002). In multivariate logistic-regression analysis, methylation of TAC1 and of the gene pair TAC1 and TACR1 was associated with an odds ratio for recurrence of 3.35 (95 % CI, 1.37-8.19; P = 0.008) and 5.09 (95 % CI, 1.44-18.02; P = 0.011), respectively.
  
  
  CONCLUSIONS
  CpG hypermethylation is a likely mechanism of TAC1 and TACR1 gene inactivation, supporting the hypothesis that TAC1 and TACR1 play a role in the tumorigenesis of HNSCC and that this hypermethylation may serve as an important biomarker.
authors: Department of Otolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Shizuoka 431-3192, Japan. kiyoshim@hama-med.ac.jp
authors: Kiyoshi
authors: K
authors: Misawa
authors: Takeharu
authors: T
authors: Kanazawa
authors: Yuki
authors: Y
authors: Misawa
authors: Atsushi
authors: A
authors: Imai
authors: Takayuki
authors: T
authors: Uehara
authors: Daiki
authors: D
authors: Mochizuki
authors: Shiori
authors: S
authors: Endo
authors: Goro
authors: G
authors: Takahashi
authors: Hiroyuki
authors: H
authors: Mineta
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D045744:Cell Line, Tumor; D019175:DNA Methylation; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D015288:Neurokinin A / Q000235:genetics*; D016017:Odds Ratio; D011379:Prognosis; D011401:Promoter Regions, Genetic; D018040:Receptors, Neurokinin-1 / Q000235:genetics*; D012008:Recurrence; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; D018040:Receptors, Neurokinin-1; D015288:Neurokinin A