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

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Abstract

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.

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Acknowledgments

The authors would like to thank Ms. Yuko Mohri for her excellent technical support. Authors received a Grant-in-Aid for Scientific Research (No. 23592524) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.

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Authors and Affiliations

  1. Department of Otolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Shizuoka, 431-3192, Japan

    Kiyoshi Misawa, Yuki Misawa, Atsushi Imai, Daiki Mochizuki, Shiori Endo, Goro Takahashi & Hiroyuki Mineta

  2. Department of Otolaryngology/Head and Neck Surgery, Jichi Medical University, Tochigi, Japan

    Takeharu Kanazawa

  3. Department of Otolaryngology/Head and Neck Surgery, University of the Ryukyus, Okinawa, Japan

    Takayuki Uehara

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  1. Kiyoshi Misawa
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Correspondence to Kiyoshi Misawa.

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Misawa, K., Kanazawa, T., Misawa, Y. et al. Frequent promoter hypermethylation of tachykinin-1 and tachykinin receptor type 1 is a potential biomarker for head and neck cancer. J Cancer Res Clin Oncol 139, 879–889 (2013). https://doi.org/10.1007/s00432-013-1393-5

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  • DOI: https://doi.org/10.1007/s00432-013-1393-5

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