title: WT1, MSH6, GATA5 and PAX5 as epigenetic oral squamous cell carcinoma biomarkers - a short report.
abstract: OBJECTIVE
  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.
authors.affiliation: Cytogenetics and Genomics Laboratory, Faculty of Medicine, University of Coimbra, Polo Ciências da Saúde, 3000-354, Coimbra, Portugal.|CIMAGO - Center of Investigation on Environment Genetics and Oncobiology - Faculty of Medicine, University of Coimbra, 3000-354, Coimbra, Portugal.
authors.forename: Ilda Patrícia
authors.initials: IP
authors.lastname: Ribeiro
authors.affiliation: Laboratory of Biostatistics and Medical Informatics, IBILI - Faculty of Medicine, University of Coimbra, 3000-354, Coimbra, Portugal.
authors.forename: Francisco
authors.initials: F
authors.lastname: Caramelo
authors.affiliation: CIMAGO - Center of Investigation on Environment Genetics and Oncobiology - Faculty of Medicine, University of Coimbra, 3000-354, Coimbra, Portugal.|Department of Dentistry, Faculty of Medicine, University of Coimbra, 3000-075, Coimbra, Portugal.|Stomatology Unit, Coimbra Hospital and University Centre (CHUC), EPE, 3000-075, Coimbra, Portugal.
authors.forename: Francisco
authors.initials: F
authors.lastname: Marques
authors.affiliation: Cytogenetics and Genomics Laboratory, Faculty of Medicine, University of Coimbra, Polo Ciências da Saúde, 3000-354, Coimbra, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Domingues
authors.affiliation: Maxillofacial Surgery Department, Coimbra Hospital and University Centre (CHUC), EPE, 3000-075, Coimbra, Portugal.
authors.forename: Margarida
authors.initials: M
authors.lastname: Mesquita
authors.affiliation: Maxillofacial Surgery Department, Coimbra Hospital and University Centre (CHUC), EPE, 3000-075, Coimbra, Portugal.
authors.forename: Leonor
authors.initials: L
authors.lastname: Barroso
authors.affiliation: Molecular Pathology Laboratory, Portuguese Institute of Oncology of Coimbra FG, EPE, 3000-075, Coimbra, Portugal.
authors.forename: Hugo
authors.initials: H
authors.lastname: Prazeres
authors.affiliation: Department of Pathology, Coimbra Hospital and University Centre (CHUC), EPE, 3000-075, Coimbra, Portugal.
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Julião
authors.affiliation: CIMAGO - Center of Investigation on Environment Genetics and Oncobiology - Faculty of Medicine, University of Coimbra, 3000-354, Coimbra, Portugal.|Department of Dentistry, Faculty of Medicine, University of Coimbra, 3000-075, Coimbra, Portugal.
authors.forename: Isabel Poiares
authors.initials: IP
authors.lastname: Baptista
authors.affiliation: Maxillofacial Surgery Department, Coimbra Hospital and University Centre (CHUC), EPE, 3000-075, Coimbra, Portugal.
authors.forename: Artur
authors.initials: A
authors.lastname: Ferreira
authors.affiliation: Cytogenetics and Genomics Laboratory, Faculty of Medicine, University of Coimbra, Polo Ciências da Saúde, 3000-354, Coimbra, Portugal.|CIMAGO - Center of Investigation on Environment Genetics and Oncobiology - Faculty of Medicine, University of Coimbra, 3000-354, Coimbra, Portugal.
authors.forename: Joana Barbosa
authors.initials: JB
authors.lastname: Melo
authors.affiliation: Cytogenetics and Genomics Laboratory, Faculty of Medicine, University of Coimbra, Polo Ciências da Saúde, 3000-354, Coimbra, Portugal. citogenetica@fmed.uc.pt.|CIMAGO - Center of Investigation on Environment Genetics and Oncobiology - Faculty of Medicine, University of Coimbra, 3000-354, Coimbra, Portugal. citogenetica@fmed.uc.pt.
authors.forename: Isabel Marques
authors.initials: IM
authors.lastname: Carreira
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D050992:GATA5 Transcription Factor / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000401:mortality; D060885:Multiplex Polymerase Chain Reaction; D051757:PAX5 Transcription Factor / Q000235:genetics*; D011379:Prognosis; D025721:WT1 Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; D050992:GATA5 Transcription Factor; C494755:GATA5 protein, human; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; D025721:WT1 Proteins; C583751:WT1 protein, human
keywords: Copy number gains and losses; DNA methylation; Oral squamous cell carcinoma; Predictors of prognosis