Abstract
Squamous cell carcinoma of the oral cavity and oropharynx is the sixth most common type of cancer in the world. During tumorigenesis, gene promoter hypermethylation is considered an important mechanism of transcription silencing of tumor suppressor genes, such as DAPK, MGMT and RUNX3. These genes participate in signaling pathways related to apoptosis, DNA repair and proliferation whose loss of expression is possibly associated with cancer development and progression. In order to investigate associations between hypermethylation and clinicopathological and prognostic parameters, promoter methylation was evaluated in 72 HPV negative oral and oropharyngeal tumors using methylation-specific PCR. Hypermethylation frequencies found for DAPK, MGMT and RUNX3 were 38.88%, 19.44% and 1.38% respectively. Patients with MGMT hypermethylation had a better 2-year overall survival compared to patients without methylation. Being MGMT a repair gene for alkylating agents, it could be a biomarker of treatment response for patients who are candidates for cisplatin chemotherapy, predicting drug resistance. In view of the considerable levels of hypermethylation in cancer cells and, for MGMT, its prognostic relevance, DAPK and MGMT show potential as epigenetic markers, in a way that additional studies may test its viability and efficacy in clinical management.
Highlights
Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of epithelial tumors that describe approximately 90% of the malignant neoplasms occurring in the oral cavity, oropharynx, hypopharynx and larynx (Pai and Westra, 2009; Hussein et al, 2017)
This study aimed to investigate the hypermethylation in death-associated protein kinase (DAPK), methylguanine DNA methyltransferase (MGMT) and RUNX3 promoter regions and their association with clinicopathological features and the prognostic overall survival and disease-free survival in Human papillomavirus (HPV)-negative oro-pharyngeal squamous cell carcinoma (OOSCC)
Hypermethylation of CpG islands in genes related to cancer has been considered an important event in OOSCC evolution
Summary
Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of epithelial tumors that describe approximately 90% of the malignant neoplasms occurring in the oral cavity, oropharynx, hypopharynx and larynx (Pai and Westra, 2009; Hussein et al, 2017). The OOSCC are very aggressive in their biologic behavior and result in a deforming and destructive disease, with frequent early lymph node metastases and potential for distant metastases over time – even after adequate local therapy (Miyazaki et al, 2006; Byakodi et al, 2012). These factors cause a significant worse prognosis and higher radio and chemotherapy morbidity (Morandi et al, 2017). Factors that contribute for this scenario are the failure in early diagnosis (two thirds are diagnosed in III–IV stages) and the lack of molecular markers that indicate tumor behavior and allow patient stratification for more personalized therapy (Mao et al, 2004; Montebugnoli et al, 2014; Morandi et al, 2017)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
