title: Identification of a combined biomarker for malignant transformation in oral submucous fibrosis.
abstract: BACKGROUND
  Oral submucous fibrosis (OSF) is a chronic progressive disease of the oral cavity that is considered a common potentially malignant disorder in South Asia. Areca nut chewing is the main etiological factor, but its carcinogenic mechanism has yet to be proven. The purpose of this study was to identify the useful biomarkers in predicting high-risk patients with OSF.
  
  
  METHODS
  Thirty-six cases of OSF and six cases of normal oral mucosa (NOM) were used for this study. Immunohistochemical staining was performed for Ki67, cyclin D1, p16, p53, β-catenin, c-Jun, c-Met, and insulin-like growth factor II mRNA-binding protein 3 (IMP3). The expression patterns of NOM served as guidelines for the scoring system.
  
  
  RESULTS
  The expression of Ki67, cyclin D1, c-Met, IMP3, and β-catenin showed a significant difference between OSF and NOM samples. The combined biomarkers of Ki67 and p16 showed significantly different expression between the transformation and non-transformation groups. With discriminant analysis, we proposed a noble formula and cutoff value for predicting high-risk patients with OSF.
  
  
  CONCLUSIONS
  The notable biomarkers in our present study were Ki67 and p16 showing significantly different expression levels between the transformation and non-transformation groups. With the identification of high-risk patients with OSF, we can expect to develop more intensive treatment modalities, leading to the reduction in cancer transformation rate from OSF.
authors: Department of Oral Pathology, Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul, South Korea.|Dental School, Mongolian National University of Medical Science, Ulaanbaatar, Mongolia.
authors: Shadavlonjid
authors: S
authors: Bazarsad
authors: Department of Oral Pathology, Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul, South Korea.|Department of Pathology, Yanbian University Hospital, Yanji, China.
authors: Xianglan
authors: X
authors: Zhang
authors: Department of Oral Pathology, Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul, South Korea.|Brain Korea 21 Plus Project, Yonsei University College of Dentistry, Seoul, South Korea.
authors: Ki-Yeol
authors: KY
authors: Kim
authors: Department of Medical Laboratory Science, Faculty of Allied Health Sciences, University of Peradeniya, Peradeniya, Sri Lanka.
authors: Rasika
authors: R
authors: Illeperuma
authors: Department of Oral Medicine & Periodontology, Faculty of Dental Sciences, University of Peradeniya, Peradeniya, Sri Lanka.
authors: Ruwan D
authors: RD
authors: Jayasinghe
authors: Department of Oral Pathology, Faculty of Dental Sciences, University of Peradeniya, Peradeniya, Sri Lanka.
authors: Wanninayake M
authors: WM
authors: Tilakaratne
authors: Department of Oral Pathology, Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul, South Korea.
authors: Jin
authors: J
authors: Kim
mesh_terms: D000328:Adult; D001114:Areca / Q000009:adverse effects; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000473:pathology*; D009914:Oral Submucous Fibrosis / Q000473:pathology*; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen
keywords: combined biomarkers; oral submucous fibrosis; risk assessment; squamous cell carcinoma