open access publication

Article, 2024

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

Cancers, ISSN 2072-6694, Volume 16, 5, Page 874, 10.3390/cancers16050874

Contributors

Sorroche, Bruna Pereira 0000-0001-9802-8236 [1] Miranda, Keila Cristina 0000-0003-1262-821X [2] Beltrami, Caroline Moraes [3] Arantes, Lidia Maria Rebolho Batista [1] Kowalski, Luiz Paulo 0000-0002-0481-156X [3] [4] Marchi, Fabio Albuquerque 0000-0001-5815-8423 [4] [5] Rogatto, Silvia Regina 0000-0003-4637-5687 [6] [7] Almeida, Janete Dias 0000-0003-4596-9715 (Corresponding author) [2]

Affiliations

  1. [1] Hospital de Câncer de Barretos
    2. [NORA names: Brazil; America, South];
  2. [2] São Paulo State University
    3. [NORA names: Brazil; America, South];
  3. [3] AC Camargo Hospital
    4. [NORA names: Brazil; America, South];
  4. [4] Universidade de São Paulo
    5. [NORA names: Brazil; America, South];
  5. [5] Instituto do Câncer do Estado de São Paulo
    6. [NORA names: Brazil; America, South];

Abstract

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 |∆β| ≥ 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.

Keywords

Atlas, Cancer Genome Atlas, CpG sites, CpGs, DNA, DNA methylation levels, DNA methylation status, Gene Expression Omnibus datasets, Genome Atlas, HOXA1, analyzed data, applications, associated with promoter methylation, biomarkers, cancer, carcinoma, cell carcinoma, clinical application, clinicopathological data, cohort, data, dataset, differentially methylated CpG sites, effect, findings, gene body methylation, gene region, genes, genomic regions, habits, head, head and neck tumors, higher methylation levels, levels, markers, methylation, methylation levels, methylation profiles, methylation status, monitoring, neck tumors, normal tissues, oral squamous cell carcinoma, oral squamous cell carcinoma patients, outcomes, overall survival, overexpression, patient monitoring, patient overall survival, patients, predictive biomarkers, profile, prognosis, prognostic biomarker, prognostic marker, prognostication, promoter, promoter methylation, pyrosequencing, radioresistance, region, samples, sites, smoking, smoking habits, squamous cell carcinoma, status, survival, tissue, tumor, tumor samples

Funders

  • São Paulo Research Foundation

Data Provider: Digital Science

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