Ilda Patrícia Ribeiro1,2, Francisco Caramelo3, Francisco Marques2,4,5, Ana Domingues1, Margarida Mesquita6, Leonor Barroso6, Hugo Prazeres7, Maria José Julião8, Isabel Poiares Baptista2,4, Artur Ferreira6, Joana Barbosa Melo1,2, Isabel Marques Carreira9,10. 1. Cytogenetics and Genomics Laboratory, Faculty of Medicine, University of Coimbra, Polo Ciências da Saúde, 3000-354, Coimbra, Portugal. 2. CIMAGO - Center of Investigation on Environment Genetics and Oncobiology - Faculty of Medicine, University of Coimbra, 3000-354, Coimbra, Portugal. 3. Laboratory of Biostatistics and Medical Informatics, IBILI - Faculty of Medicine, University of Coimbra, 3000-354, Coimbra, Portugal. 4. Department of Dentistry, Faculty of Medicine, University of Coimbra, 3000-075, Coimbra, Portugal. 5. Stomatology Unit, Coimbra Hospital and University Centre (CHUC), EPE, 3000-075, Coimbra, Portugal. 6. Maxillofacial Surgery Department, Coimbra Hospital and University Centre (CHUC), EPE, 3000-075, Coimbra, Portugal. 7. Molecular Pathology Laboratory, Portuguese Institute of Oncology of Coimbra FG, EPE, 3000-075, Coimbra, Portugal. 8. Department of Pathology, Coimbra Hospital and University Centre (CHUC), EPE, 3000-075, Coimbra, Portugal. 9. Cytogenetics and Genomics Laboratory, Faculty of Medicine, University of Coimbra, Polo Ciências da Saúde, 3000-354, Coimbra, Portugal. citogenetica@fmed.uc.pt. 10. CIMAGO - Center of Investigation on Environment Genetics and Oncobiology - Faculty of Medicine, University of Coimbra, 3000-354, Coimbra, Portugal. citogenetica@fmed.uc.pt.
Abstract
PURPOSE: Oral squamous cell carcinoma (OSCC) is a frequently occurring aggressive malignancy with a heterogeneous clinical behavior. Based on the paucity of specific early diagnostic and prognostic biomarkers, which hampers the appropriate treatment and, ultimately the development of novel targeted therapies, we aimed at identifying such biomarkers through a genetic and epigenetic analysis of these tumors. METHODS: 93 primary OSCCs were subjected to DNA copy number alteration (CNA) and methylation status analyses using methylation-specific multiplex ligation-dependent probe amplification (MS-MPLA). The genetic and epigenetic OSCC profiles obtained were associated with the patients' clinic-pathological features. RESULTS: We found that WT1 gene promoter methylation is a predictor of a better prognosis and that MSH6 and GATA5 gene promoter methylation serve as predictors of a worse prognosis. GATA5 gene promoter methylation was found to be significantly associated with a shorter survival rate. In addition, we found that PAX5 gene promoter methylation was significantly associated with tongue tumors. To the best of our knowledge, this is the first study that highlights this specific set of genes as epigenetic diagnostic and prognostic biomarkers in OSCC. CONCLUSIONS: Our data highlight the importance of epigenetically assessing OSCCs to identify key genes that may serve as diagnostic and prognostic biomarkers and, potentially, as candidate therapeutic targets.
PURPOSE:Oral squamous cell carcinoma (OSCC) is a frequently occurring aggressive malignancy with a heterogeneous clinical behavior. Based on the paucity of specific early diagnostic and prognostic biomarkers, which hampers the appropriate treatment and, ultimately the development of novel targeted therapies, we aimed at identifying such biomarkers through a genetic and epigenetic analysis of these tumors. METHODS: 93 primary OSCCs were subjected to DNA copy number alteration (CNA) and methylation status analyses using methylation-specific multiplex ligation-dependent probe amplification (MS-MPLA). The genetic and epigenetic OSCC profiles obtained were associated with the patients' clinic-pathological features. RESULTS: We found that WT1 gene promoter methylation is a predictor of a better prognosis and that MSH6 and GATA5 gene promoter methylation serve as predictors of a worse prognosis. GATA5 gene promoter methylation was found to be significantly associated with a shorter survival rate. In addition, we found that PAX5 gene promoter methylation was significantly associated with tongue tumors. To the best of our knowledge, this is the first study that highlights this specific set of genes as epigenetic diagnostic and prognostic biomarkers in OSCC. CONCLUSIONS: Our data highlight the importance of epigenetically assessing OSCCs to identify key genes that may serve as diagnostic and prognostic biomarkers and, potentially, as candidate therapeutic targets.
Entities:
Keywords:
Copy number gains and losses; DNA methylation; Oral squamous cell carcinoma; Predictors of prognosis
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