neurokinin-a and Head-and-Neck-Neoplasms

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.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Cell Line, Tumor; DNA Methylation; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Neoplasm Staging; Neurokinin A; Odds Ratio; Prognosis; Promoter Regions, Genetic; Receptors, Neurokinin-1; Recurrence; Risk Factors