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

Misawa, Kiyoshi; Kanazawa, Takemichi; Misawa, Yuki; Imai, Atsushi; Uehara, Takayuki; Mochizuki, Daiki; Endo, Shiori; Takahashi, Goro; Mineta, Hiroyuki

doi:10.1007/s00432-013-1393-5

Cited by 26 publications

(32 citation statements)

References 33 publications

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“…Such knowledge could carry importance in a clinical setting, for example, to predict either prognosis and/or a treatment response with NK1R antagonists. Such a correlation has been described for the expression rate of the SP/NK1R complex and prognosis in other pediatric tumors (110,(152)(153)(154). For example, Garcia-Recio et al found that SP contributes to persistent transmodulation of the ErbB receptors, EGFR and HER2, in breast cancer, where it enhances malignancy and therapeutic resistance (110).…”

Section: The Nk1r As An Anti-tumor Target In Hepatoblastoma In the CLmentioning

confidence: 85%

Therapeutic Innovations for Targeting Hepatoblastoma

Garnier

Ilmer

Kappler

et al. 2016

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Section: The Nk1r As An Anti-tumor Target In Hepatoblastoma In the CLmentioning

confidence: 85%

Therapeutic Innovations for Targeting Hepatoblastoma

Garnier

Ilmer

Kappler

et al. 2016

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“…It has previously been proposed that a correlation exists between the expression rate of the NK1R/SP complex and prognosis in various types of cancer (18)(19)(20)(21)(22). Garcia-Recio et al identified that SP contributes to persistent transmodulation of the ErbB receptors, epidermal growth factor receptor (EGFR) and human epidermal growth factor 2 (HER2), in breast cancer, acting to enhance malignancy and therapeutic resistance.…”

Section: Discussionmentioning

confidence: 99%

“…Notably, this signature discriminates invasive and metastatic from localized HB and predicts prognosis with high accuracy (16). Additionally, it has recently been suggested that the expression of TACR1 may correlate with a clinically worse prognosis in some cancers (18)(19)(20)(21)(22). However, scientific evidence for such an association remains scarce.…”

Section: Introductionmentioning

confidence: 99%

Truncated neurokinin-1 receptor is an ubiquitous antitumor target in hepatoblastoma, and its expression is independent of tumor biology and stage

et al. 2015

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Abstract. The substance P (SP; also known as TAC1)/neurokinin-1 receptor (NK1R; also known as TACR1) complex is a critical part in the development of cancer. Therefore, NK1R antagonists, such as the clinical drug aprepitant, are currently under investigation as future anticancer agents. In a previous study, NK1R (TACR1) was identified as a potent anticancer target in hepatoblastoma (HB). However, little is known regarding the exact distribution of this target among HB subsets and whether it correlates with clinical features and prognosis. In the present study, mRNA was isolated from 47 children with HB, and reverse transcription-quantitative polymerase chain reaction was performed on the samples to analyze the expression of full-length-TACR1 (fl-TACR1) and truncated-TACR1 (tr-TACR1). These data were correlated with data obtained from 9 tumor-free controls, as well as with the presence of metastasis, PRETEXT, vascular invasion, histology, age of diagnosis, multifocality, CTNNB1 mutation, gender and overall survival. Additionally, the present study investigated a recently described 16-gene signature characteri zing HB known to correlate with prognosis. Compared with tumor-free liver tissue, tumorous tissue expressed TACR1 significantly higher for the truncated version (P=0.0301), and by trend also for the full-length version. Accordingly, the expression of fl-TACR1 correlated with the expression of the truncated version (P=0.0074). Furthermore, a low expression of fl-TACR1 correlated with characteristics of the 16-gene signature known to predict prognosis (P=0.0222). However, there was no correlation between tr-TACR1 and the tumor characteristics investigated, including outcome, although a clear trend was observed for some tumor characteristics. The current results reinforced the previously described findings that in HB, tr-TACR1 is overexpressed compared with tumor-free liver tissue. Furthermore, to the best of our knowledge, the present study demonstrated for the first time that tr-TACR1 is expressed ubiquitously among the different subsets of HB. Therefore, NK1R may serve as a potent anticancer target in a large variety of patients with HB, independent of tumor biology and clinical stage.

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“…More recently, data from our laboratory have shown that the galanin , GALR1 , GALR2 , TAC1 , and TACR1 promoters are methylated in HNSCC. [15,16] Therefore, we hypothesized that neuropeptide genes and receptor genes might be inactivated via promoter hypermethylation in human head and neck cancers, and that hypermethylation of these genes is an important event in the genesis of HNSCC. Moreover, we discovered a unique inverse relationship between SST and SSTR1 -promoter hypermethylation and other neuropeptide genes.…”

Section: Introductionmentioning

confidence: 99%

Aberrant Methylation Inactivates Somatostatin and Somatostatin Receptor Type 1 in Head and Neck Squamous Cell Carcinoma

Misawa

Kondo

et al. 2015

PLoS ONE

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PurposeThe aim of this study was to define somatostatin (SST) and somatostatin receptor type 1 (SSTR1) 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.MethodsGene expression was measured by quantitative RT-PCR. Promoter methylation status was determined by quantitative methylation-specific PCR (Q-MSP) in HNSCC.ResultsMethylation was associated with transcription inhibition. SST methylation in 81% of HNSCC tumor specimens significantly correlated with tumor size (P = 0.043), stage (P = 0.008), galanin receptor type 2 (GALR2) methylation (P = 0.041), and tachykinin-1 (TAC1) (P = 0.040). SSTR1 hypermethylation in 64% of cases was correlated with tumor size (P = 0.037), stage (P = 0.037), SST methylation (P < 0.001), and expression of galanin (P = 0.03), GALR2 (P = 0.014), TAC1 (P = 0.023), and tachykinin receptor type 1 (TACR1) (P = 0.003). SST and SSTR1 promoter hypermethylation showed highly discriminating receiver operator characteristic curve profiles, which clearly distinguished HNSCC from adjacent normal mucosal tissues. Concurrent hypermethylation of galanin and SSTR1 promoters correlated with reduced disease-free survival (log-rank test, P = 0.0001). Among patients with oral cavity and oropharynx cancer, methylation of both SST and SSTR1 promoters correlated with reduced disease-free survival (log-rank test, P = 0.028). In multivariate logistic-regression analysis, concomitant methylation of galanin and SSTR1 was associated with an odds ratio for recurrence of 12.53 (95% CI, 2.62 to 59.8; P = 0.002).ConclusionsCpG hypermethylation is a likely mechanism of SST and SSTR1 gene inactivation, supporting the hypothesis that SST and SSTR1 play a role in the tumorigenesis of HNSCC and that this hypermethylation may serve as an important biomarker.

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

Abstract: 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.

Cited by 26 publications

References 33 publications

Therapeutic Innovations for Targeting Hepatoblastoma

Therapeutic Innovations for Targeting Hepatoblastoma

Truncated neurokinin-1 receptor is an ubiquitous antitumor target in hepatoblastoma, and its expression is independent of tumor biology and stage

Aberrant Methylation Inactivates Somatostatin and Somatostatin Receptor Type 1 in Head and Neck Squamous Cell Carcinoma

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