title: Hypermethylated ZNF582 and PAX1 are effective biomarkers for detection of oral dysplasia and oral cancer.
abstract: This study investigated whether the methylation of ZNF582, PAX1, SOX1, NKX6.1, and PTPRR genes in oral scrapings could be used to detect oral dysplasia and oral cancer and to predict oral cancer recurrence.
  
  
  
  Oral scrapings were collected from 65 normal oral mucosa subjects, 107 oral precancer patients, and 95 oral squamous cell carcinoma patients. Methylation levels of the five genes were quantified by real-time methylation-specific PCR after bisulfite conversion.
  
  
  
  Among the five tested genes, methylated ZNF582 (ZNF582m) and PAX1 (PAX1m) were found to be appropriate biomarkers for oral dysplasia and oral cancers. ZNF582mcould detect mild dysplasia or worse oral lesions with the sensitivity and specificity being 0.85 and 0.87, respectively. PAX1mperformed better in identifying moderate dysplasia or worse oral lesions with the sensitivity and specificity being 0.72 and 0.86, respectively. Moreover, the methylation levels and positive rates for ZNF582mand PAX1mwere increased when disease severity increased. Thus, they may be applicable as a triage tool for patients with abnormal visual oral examinations. After cancer excision, both ZNF582mand PAX1mlevels decreased. However, their levels increased again at the subsequently recurrent sites in some patients approximately 3-4 months before cancer recurrence. Finally, areca-quid chewing alone and in combination with cigarette smoking or alcohol drinking were found to be correlated with ZNF582 and PAX1 hypermethylation.
  
  
  
  We conclude that hypermethylated ZNF582 and PAX1 are effective biomarkers for the detection of oral dysplasia and oral cancer and for the prediction of oral cancer recurrence.
authors.affiliation: Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, College of Medicine, Taipei, Taiwan; Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan.
authors.forename: Shih-Jung
authors.initials: SJ
authors.lastname: Cheng
authors.affiliation: iStat Biomedical Co., Ltd, New Taipei City, Taiwan; Academia-Industry Bridging Program (AIBP), National Research Program for Bio-pharmaceuticals, Taipei, Taiwan.
authors.forename: Chi-Feng
authors.initials: CF
authors.lastname: Chang
authors.affiliation: Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, College of Medicine, Taipei, Taiwan; Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan.
authors.forename: Jang-Jaer
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, College of Medicine, Taipei, Taiwan; Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan.
authors.forename: Hsin-Ming
authors.initials: HM
authors.lastname: Chen
authors.affiliation: iStat Biomedical Co., Ltd, New Taipei City, Taiwan.
authors.forename: Huei-Jen
authors.initials: HJ
authors.lastname: Wang
authors.affiliation: iStat Biomedical Co., Ltd, New Taipei City, Taiwan.
authors.forename: Yu-Ligh
authors.initials: YL
authors.lastname: Liou
authors.affiliation: iStat Biomedical Co., Ltd, New Taipei City, Taiwan; Department of Molecular and Cell Biology, University of California, Berkeley, CA, United States.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Yen
authors.affiliation: Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, College of Medicine, Taipei, Taiwan; Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan. Electronic address: cpchiang@ntu.edu.tw.
authors.forename: Chun-Pin
authors.initials: CP
authors.lastname: Chiang
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D019175:DNA Methylation; D005260:Female; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D009364:Neoplasm Recurrence, Local; D051761:Paired Box Transcription Factors / Q000235:genetics*; D011230:Precancerous Conditions / Q000175:diagnosis* / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D051741:Kruppel-Like Transcription Factors; D051761:Paired Box Transcription Factors; C577358:ZNF582 protein, human; C070835:PAX1 transcription factor
keywords: DNA methylation biomarker; Oral cancer; Oral dysplasia; PAX1; ZNF582