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

• Published in: Journal of cancer research and clinical oncology Vol. 139; no. 5; pp. 879 - 889
• Main Authors: Misawa, Kiyoshi, Kanazawa, Takeharu, Misawa, Yuki, Imai, Atsushi, Uehara, Takayuki, Mochizuki, Daiki, Endo, Shiori, Takahashi, Goro, Mineta, Hiroyuki
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.05.2013; Springer; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic agents; Biological and medical sciences; Biomarkers; Biomarkers, Tumor - genetics; Cancer Research; Cell Line, Tumor; DNA Methylation; Female; Genes; Head & neck cancer; Head and Neck Neoplasms - genetics; Head and Neck Neoplasms - mortality; Head and Neck Neoplasms - pathology; Hematology; Humans; Internal Medicine; Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasm Staging; Neurokinin A - genetics; Odds Ratio; Oncology; Original Paper; Otorhinolaryngology (head neck, general aspects and miscellaneous); Otorhinolaryngology. Stomatology; Pharmacology. Drug treatments; Prognosis; Promoter Regions, Genetic; Receptors, Neurokinin-1 - genetics; Recurrence; Risk Factors; Tumors; DNA methylation; Head and neck cancer; TACR1; Galanin; TAC1; Transcription promoter; Biological marker; Malignant tumor; Neuropeptide; DNA; ENT disease; Frequency; Tachykinin receptor; Methylation; Tachykinin; Cancer
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-013-1393-5

Aim 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. Materials and 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. Conclusion 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.