Neuropeptide receptor genes GHSR and NMUR1 are candidate epigenetic biomarkers and predictors for surgically treated patients with oropharyngeal cancer.

Abstract

Pathological staging and histological grading systems are useful, but imperfect, predictors of recurrence in head and neck squamous cell carcinoma (HNSCC). Aberrant promoter methylation is the main type of epigenetic modification that plays a role in the inactivation of tumor suppressor genes. To identify new potential prognostic markers, we investigated the promoter methylation status of five neuropeptide receptor genes. The methylation status of the target genes was compared with clinical characteristics in 278 cases; 72 hypopharyngeal cancers, 54 laryngeal cancers, 75 oropharyngeal cancers, and 77 oral cavity cancers were studied. We found that the NTSR1, NTSR2, GHSR, MLNR, and NMUR1 promoters were methylated in 47.8%, 46.8%, 54.3%, 39.2%, and 43.5% of the samples, respectively. GHSR and NMUR1 promoter methylation independently predicted recurrence in HNSCC. In patients with oropharyngeal cancer (n = 75), GHSR and NMUR1 promoter methylation significantly correlates with survival in surgically treated patients. We classified our patients as having a low, intermediate, or high-risk of death based on three factors: HPV status, and GHSR and NMUR1 promoter methylation. The disease-free survival (DFS) rates were 87.1%, 42.7%, and 17.0%, respectively. Combined data analysis of the methylation status of ten-eleven translocation (TET) family genes indicated a trend toward greater methylation indices as the number of TET methylation events increased. In the current study, we presented the relationship between the methylation status of the GHSR and NMUR1 genes and recurrence in HNSCC, specifically in risk classification of oropharyngeal carcinomas cases with HPV status.

• Authors: Kiyoshi Misawa, Masato Mima, Yamada Satoshi, Yuki Misawa, Atsushi Imai, Daiki Mochizuki, Takuya Nakagawa, Tomoya Kurokawa, Miki Oguro, Ryuji Ishikawa, Yuki Yamaguchi, Shiori Endo, Hideya Kawasaki, Takeharu Kanazawa, Hiroyuki Mineta
• Journal: Scientific reports (Sci Rep) Vol. 10 Issue 1 Pg. 1007 (01 23 2020) ISSN: 2045-2322 [Electronic] England
• PMID: 31974445 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• DNA-Binding Proteins
• NMUR1 protein, human
• Proto-Oncogene Proteins
• Receptors, Ghrelin
• Receptors, Neurotransmitter
• Mixed Function Oxygenases
• TET1 protein, human
• TET3 protein, human
• Dioxygenases
• TET2 protein, human

Topics

• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (genetics)
• DNA Methylation (genetics)
• DNA-Binding Proteins (genetics)
• Dioxygenases (genetics)
• Disease-Free Survival
• Female
• Humans
• Male
• Middle Aged
• Mixed Function Oxygenases (genetics)
• Neoplasm Recurrence, Local (genetics)
• Neoplasm Staging
• Oropharyngeal Neoplasms (genetics, pathology, surgery)
• Promoter Regions, Genetic (genetics)
• Proto-Oncogene Proteins (genetics)
• Receptors, Ghrelin (genetics)
• Receptors, Neurotransmitter (genetics)
• Squamous Cell Carcinoma of Head and Neck (genetics, pathology, surgery)