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Promoter methylation of galanin receptors as epigenetic biomarkers for head and neck squamous cell carcinomas
Authors:Takeharu Kanazawa  Kiyoshi Misawa  Kazuya Shinmura  Yuki Misawa  Gen Kusaka  Mikiko Maruta
Affiliation:1. Department of Otolaryngology-Head and Neck Surgery, International University of Health and Welfare, Tokyo, Japan;2. Department of Otolaryngology-Head and Neck Surgery, Jichi Medical University, Shimotsuke, Japan;3. Department of Otolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan;4. Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan;5. Department of Neurosurgery, Jichi Medical University Saitama Medical Center, Saitama, Saitama, Japan;6. Department of Otolaryngology-Head and Neck Surgery, Jichi Medical University, Shimotsuke, Japan
Abstract:Introduction: While remarkable progress has been made in standard treatments for head and neck squamous cell carcinomas (HNSCCs), the long-term survival remains at an unsatisfactory 40–50%. To improve the survival rate, biomarkers for optimal treatment selection and prognostic prediction, as well as novel, low-toxicity treatment strategies, are required. Galanin receptor (GALR) 1 and GALR2 are well-studied tumor suppressors in HNSCCs. Compared with other clinicopathological factors, the epigenetic variants of GALRs have been found to be the most powerful markers to predict the prognosis of HNSCC patients.

Areas covered: This review outlines the functions and signaling pathways of GALRs and explains the potential of GALR promoter methylation as a biomarker for HNSCC prognosis. We also summarize recent developments in promoter methylation studies in HNSCC and indicate future directions for GALR promoter methylation studies.

Expert commentary: GALR studies have highlighted two major aspects with implications in HNSCC – that G-protein coupled receptors (GPCRs) act as tumor suppressor genes and that GALR promoter methylation is significantly related to the carcinogenesis of HNSCC. The findings of GALR studies can be applied to studies on other GPCRs and further in-depth DNA methylation studies. Deeper insights into GPCR epigenetics are expected to markedly improve HNSCC treatment.

Keywords:Biomarker  epigenetics  G-protein coupled receptor  head and neck neoplasm  molecular targeted treatment
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