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

Cell Oncol (Dordr). 2016 Dec;39(6):573-582. doi: 10.1007/s13402-016-0293-5. Epub 2016 Aug 4.

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.

Keywords: Copy number gains and losses; DNA methylation; Oral squamous cell carcinoma; Predictors of prognosis.

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / mortality
  • DNA Methylation
  • DNA-Binding Proteins / genetics*
  • Epigenesis, Genetic
  • Female
  • GATA5 Transcription Factor / genetics*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Mouth Neoplasms / genetics*
  • Mouth Neoplasms / mortality
  • Multiplex Polymerase Chain Reaction
  • PAX5 Transcription Factor / genetics*
  • Prognosis
  • WT1 Proteins / genetics*

Substances

  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • G-T mismatch-binding protein
  • GATA5 Transcription Factor
  • GATA5 protein, human
  • PAX5 Transcription Factor
  • PAX5 protein, human
  • WT1 Proteins
  • WT1 protein, human