Frequent promoter hypermethylation of tachykinin-1 and tachykinin receptor type 1 is a potential biomarker for head and neck cancer

• DOI: 10.1007/s00432-013-1393-5
• Publication Date: 2013-02-18T22:48:53Z
• Authors: Kiyoshi Misawa; Takeharu Kanazawa; Yuki Misawa; Atsushi Imai; Takayuki Uehara; Daiki Mochizuki; Shiori Endo; Goro Takahashi; Hiroyuki Mineta
• Keywords: Adult; Aged, 80 and over; Male; 0301 basic medicine; Neurokinin A; DNA Methylation; Middle Aged; Receptors, Neurokinin-1; Prognosis; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Head and Neck Neoplasms; Recurrence; Risk Factors; Cell Line, Tumor; Biomarkers, Tumor; Odds Ratio; Humans; Female; Promoter Regions, Genetic; Aged; Neoplasm Staging

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.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.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.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.