Investigation of the methylation profile as a prognostic indicator in head and neck cancer

• Grant number: 24/22868-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: July 01, 2025
• End date: June 30, 2028
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Lidia Maria Rebolho Batista Arantes
• Grantee: Paula Roberta Aguiar Pastrez
• Host Institution: Hospital do Câncer de Barretos. Fundação Pio XII (FP). Barretos , SP, Brazil
• Associated research grant: 22/03556-9 - Identification of non-invasive methods for the early diagnosis of squamous cell carcinoma of the oral cavity and oropharynx, AP.TEM

Abstract

Head and neck cancer is a disease with high incidence and mortality, primarily affecting the oral cavity, pharynx, and larynx. Most cases are detected at advanced stages and are associated with low survival rates, frequent recurrences, and poor prognosis, which underscores the importance of early diagnosis to improve clinical outcomes. It is a multifactorial disease, involving both genetic and epigenetic factors, with DNA methylation being a relevant mechanism for tumor progression. Methylation changes, such as hypermethylation in promoter regions, can silence tumor suppressor genes or activate oncogenes, contributing to tumorigenesis. Studies suggest that methylation biomarkers can be used for early detection and to monitor disease prognosis. Hypermethylation, in particular, is associated with disease severity and metastatic potential. The proposed project aims to determine the methylation profile in pre-neoplastic lesions (erythroplakia and leukoplakia) and early-stage head and neck cancer, without lymph node metastasis, in the oral cavity and oropharynx, using global methylation analysis. The goal is to establish the association between the identified methylation profile and cellular transformation, disease progression, and patient prognosis. For this, DNA will be extracted from cryopreserved material collected from participants, followed by sodium bisulfite treatment, and the samples will undergo global methylation analysis. The methylation array will be analyzed using bioinformatics, and the key targets identified will be validated through liquid biopsy. Finally, the percentage of methylated cytosines in CpG-rich regions will be quantified through DNA sequencing using the pyrosequencing system. (AU)