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HOXA1 3′UTR Methylation Is a Potential Prognostic Biomarker in Oral Squamous cell Carcinoma

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Autor(es):
Sorroche, Bruna Pereira ; Miranda, Keila Cristina ; Beltrami, Caroline Moraes ; Arantes, Lidia Maria Rebolho Batista ; Kowalski, Luiz Paulo ; Marchi, Fabio Albuquerque ; Rogatto, Silvia Regina ; Almeida, Janete Dias
Número total de Autores: 8
Tipo de documento: Artigo Científico
Fonte: CANCERS; v. 16, n. 5, p. 14-pg., 2024-03-01.
Resumo

Simple Summary: Head and neck cancer with increased expression levels of HOXA1 tends to have a worse outcome. This gene is regulated by DNA methylation. Herein, we studied the methylation pattern of HOXA1 in oral cavity tumors. We found that methyl groups gather more often in a specific region of HOXA1, named 3 ' UTR, in tumor cells compared to healthy tissues. Interestingly, patients with increased methylation levels were preferentially detected in heavier smokers and patients with a longer survival. Our findings suggest that the analysis of the DNA methylation located in the 3 ' UTR of HOXA1 could help predict the patient's prognosis. Our findings could potentially guide treatment decisions and improve patient care in the future. Background: HOXA1 is a prognostic marker and a potential predictive biomarker for radioresistance in head and neck tumors. Its overexpression has been associated with promoter methylation and a worse prognosis in oral squamous cell carcinoma (OSCC) patients. However, opposite outcomes are also described. The effect of the methylation of this gene on different gene regions, other than the promoter, remains uncertain. We investigated the methylation profile at different genomic regions of HOXA1 in OSCC and correlated differentially methylated CpG sites with clinicopathological data. Methods: The HOXA1 DNA methylation status was evaluated by analyzing data from The Cancer Genome Atlas and three Gene Expression Omnibus datasets. Significant differentially methylated CpG sites were considered with a |triangle beta| >= 0.10 and a Bonferroni-corrected p-value < 0.01. Differentially methylated CpGs were validated by pyrosequencing using two independent cohorts of 15 and 47 OSCC patients, respectively. Results: Compared to normal tissues, we found significantly higher DNA methylation levels in the 3 ' UTR region of HOXA1 in OSCC. Higher methylation levels in tumor samples were positively correlated with smoking habits and patients' overall survival. Conclusions: Our findings suggest that HOXA1 gene body methylation is a promising prognostic biomarker for OSCC with potential clinical applications in patient monitoring. (AU)

Processo FAPESP: 16/08633-0 - Tabagismo: dos aspectos moleculares a abordagem do fumante
Beneficiário:Janete Dias Almeida
Modalidade de apoio: Auxílio à Pesquisa - Regular