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WT1, MSH6, GATA5 and PAX5 as epigenetic oral squamous cell carcinoma biomarkers - a short report

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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.

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Acknowledgments

Ribeiro I.P. is a recipient of a PhD fellowship (SFRH/BD/52290/2013) from the Portuguese Foundation for Science and Technology. This work was in part supported by CIMAGO (Center of Investigation on Environment Genetics and Oncobiology - Faculty of Medicine, University of Coimbra) and by the Portuguese Foundation for Science and Technology (grant: UID/NEU/04539/2013).

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Authors and Affiliations

  1. Cytogenetics and Genomics Laboratory, Faculty of Medicine, University of Coimbra, Polo Ciências da Saúde, 3000-354, Coimbra, Portugal

    Ilda Patrícia Ribeiro, Ana Domingues, Joana Barbosa Melo & Isabel Marques Carreira

  2. CIMAGO - Center of Investigation on Environment Genetics and Oncobiology - Faculty of Medicine, University of Coimbra, 3000-354, Coimbra, Portugal

    Ilda Patrícia Ribeiro, Francisco Marques, Isabel Poiares Baptista, Joana Barbosa Melo & Isabel Marques Carreira

  3. Laboratory of Biostatistics and Medical Informatics, IBILI - Faculty of Medicine, University of Coimbra, 3000-354, Coimbra, Portugal

    Francisco Caramelo

  4. Department of Dentistry, Faculty of Medicine, University of Coimbra, 3000-075, Coimbra, Portugal

    Francisco Marques & Isabel Poiares Baptista

  5. Stomatology Unit, Coimbra Hospital and University Centre (CHUC), EPE, 3000-075, Coimbra, Portugal

    Francisco Marques

  6. Maxillofacial Surgery Department, Coimbra Hospital and University Centre (CHUC), EPE, 3000-075, Coimbra, Portugal

    Margarida Mesquita, Leonor Barroso & Artur Ferreira

  7. Molecular Pathology Laboratory, Portuguese Institute of Oncology of Coimbra FG, EPE, 3000-075, Coimbra, Portugal

    Hugo Prazeres

  8. Department of Pathology, Coimbra Hospital and University Centre (CHUC), EPE, 3000-075, Coimbra, Portugal

    Maria José Julião

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  1. Ilda Patrícia Ribeiro
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  2. Francisco Caramelo
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Correspondence to Isabel Marques Carreira.

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The authors have no conflict of interest to disclose.

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Ilda Patrícia Ribeiro and Francisco Caramelo contributed equally to this work.

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Ribeiro, I.P., Caramelo, F., Marques, F. et al. WT1, MSH6, GATA5 and PAX5 as epigenetic oral squamous cell carcinoma biomarkers - a short report. Cell Oncol. 39, 573–582 (2016). https://doi.org/10.1007/s13402-016-0293-5

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