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.

The Pre-Treatment C-Reactive Protein Represents a Prognostic Factor in Patients with Oral and Oropharyngeal Cancer Treated with Radiotherapy

“…During recent years, a large number of translational research studies have revealed an association of various molecular biomarkers with clinical outcome in OOSCC. Molecular predictors of prognosis (e.g., DNA methylation markers or miRNA expression) may provide additional prognostic and/or predictive information, but high costs, lack of standardization and regional availability limit their application in routine clinical practice [3,4].…”

Rare deleterious germline variants and risk of lung cancer

“…MLNR is a member of the G-protein coupled receptor 1 family, and known for regulating gastrointestinal activity 70 . MLNR variants and dysregulation have been implicated in lung occult small cell carcinoma, bile duct cancer 71 , and head and neck cancer 72 . Our overproduction results of the MLNR p.Q334V fs*3del suggest a dominant-negative role in terms of DNA damage promotion.…”

Identification of novel methylation markers in HPV-associated oropharyngeal cancer: genome-wide discovery, tissue verification and validation testing in ctDNA

“…The biomarkers we describe have the potential to affect one of the most important unmet clinical needs in HPVassociated OPC: a risk classification system that is more effective than patient history and physical examination [14]. The advantages of our study are the evaluation of a large, independent series of different patient-derived sample types, and the use of a discovery-verification-validation approach, which allowed us to evaluate the succession of methylation events and the selection of methylation targets which are prognostically relevant and associated with HPV-associated carcinogenesis.…”