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Updated: Apr 16, 2026

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
Published on: August 5, 2022
Aberrant methylation inactivates somatostatin and somatostatin receptor type 1 in head and neck squamous cell
Kiyoshi Misawa1, Yuki Misawa1, Haruki Kondo1
1Department of Otolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan.
Purpose:
The 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.
Methods:
Gene expression was measured by quantitative RT-PCR. Promoter methylation status was determined by quantitative methylation-specific PCR (Q-MSP) in HNSCC.
Results:
Methylation 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).
Conclusions:
CpG 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.
Insights
CpG hypermethylation of somatostatin (SST) and somatostatin receptor type 1 (SSTR1) genes inactivates their function in head and neck squamous cell carcinoma (HNSCC). This hypermethylation serves as a potential biomarker for HNSCC diagnosis and prognosis.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Head and neck squamous cell carcinoma (HNSCC) is a prevalent cancer with complex molecular underpinnings.
- Understanding epigenetic modifications like DNA methylation is crucial for identifying novel biomarkers and therapeutic targets in HNSCC.
Purpose of the Study:
- To investigate the methylation profiles of somatostatin (SST) and somatostatin receptor type 1 (SSTR1) in HNSCC.
- To assess the prognostic significance and diagnostic value of SST and SSTR1 methylation in HNSCC.
Main Methods:
- Quantitative RT-PCR was used to measure gene expression.
- Quantitative methylation-specific PCR (Q-MSP) determined promoter methylation status in HNSCC tumor samples and adjacent normal tissues.
Main Results:
- SST methylation (81% of tumors) and SSTR1 hypermethylation (64% of tumors) were frequently observed and associated with tumor stage and size.
- Both SST and SSTR1 promoter hypermethylation clearly distinguished HNSCC from normal tissues.
- Concurrent hypermethylation of SST and SSTR1 promoters correlated with reduced disease-free survival and increased risk of recurrence in HNSCC patients.
Conclusions:
- CpG hypermethylation is a key mechanism for SST and SSTR1 gene inactivation in HNSCC.
- These methylation events suggest a role for SST and SSTR1 in HNSCC tumorigenesis.
- SST and SSTR1 promoter hypermethylation represent promising biomarkers for HNSCC.
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07:29Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
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