title: The high-temperature requirement factor A3 (HtrA3) is associated with acquisition of the invasive phenotype in oral squamous cell carcinoma cells.
abstract: OBJECTIVE
  Previous studies have identified several genes involved in the carcinogenesis of oral cancer; however, the detailed mechanisms underlying this process have not been elucidated. Previously, we established a database of the transcriptional progression profile of oral carcinogenesis and identified 15 candidate genes with continuously increasing or decreasing expression (Sumino et al., 2013).
  
  
  METHODS
  In the present study, using this database, we attempted to identify genes that may specifically contribute to progression from oral dysplastic lesions to invasive tumours.
  
  
  RESULTS
  We identified 4 candidate genes. Using a literature survey, we narrowed down the candidates and focused on the high-temperature requirement factor A3 (HtrA3). Quantitative real-time reverse transcription polymerase chain reaction and immunohistochemical analysis confirmed that HtrA3 expression significantly increased during this process. In addition, high HtrA3 expression was significantly associated with decreased disease-free survival (P=0.045) and overall survival (P=0.003). Multivariate Cox proportional hazards analysis found that high HtrA3 expression significantly correlated with overall survival (P=0.018).
  
  
  CONCLUSIONS
  The findings of this study demonstrated that the HtrA3 is likely to be associated with the acquisition of the invasive phenotype in oral squamous cell carcinoma cells and may be a potential prognostic marker for oral cancer.
authors.affiliation: Maxillofacial Surgery, Maxillofacial Reconstruction and Function, Division of Maxillofacial and Neck Reconstruction, Tokyo Medical and Dental University, Tokyo, Japan. Electronic address: 1022mfs@tmd.ac.jp.
authors.forename: Yujiro
authors.initials: Y
authors.lastname: Moriya
authors.affiliation: Maxillofacial Surgery, Maxillofacial Reconstruction and Function, Division of Maxillofacial and Neck Reconstruction, Tokyo Medical and Dental University, Tokyo, Japan. Electronic address: n-uzawa.mfs@tmd.ac.jp.
authors.forename: Narikazu
authors.initials: N
authors.lastname: Uzawa
authors.affiliation: Maxillofacial Surgery, Maxillofacial Reconstruction and Function, Division of Maxillofacial and Neck Reconstruction, Tokyo Medical and Dental University, Tokyo, Japan. Electronic address: morimfs@tmd.ac.jp.
authors.forename: Takuma
authors.initials: T
authors.lastname: Morita
authors.affiliation: Department of Computational Biology, Graduate School of Biomedical Science, Tokyo Medical and Dental University, Tokyo, Japan. Electronic address: mogushi@bioinfo.tmd.ac.jp.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Mogushi
authors.affiliation: Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan. Electronic address: miyaguchi@bioinfo.tmd.ac.jp.
authors.forename: Ken
authors.initials: K
authors.lastname: Miyaguchi
authors.affiliation: Maxillofacial Surgery, Maxillofacial Reconstruction and Function, Division of Maxillofacial and Neck Reconstruction, Tokyo Medical and Dental University, Tokyo, Japan. Electronic address: ken514.mfs@tmd.ac.jp.
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Maxillofacial Surgery, Maxillofacial Reconstruction and Function, Division of Maxillofacial and Neck Reconstruction, Tokyo Medical and Dental University, Tokyo, Japan. Electronic address: c-michikawa.mfs@tmd.ac.jp.
authors.forename: Chieko
authors.initials: C
authors.lastname: Michikawa
authors.affiliation: Maxillofacial Surgery, Maxillofacial Reconstruction and Function, Division of Maxillofacial and Neck Reconstruction, Tokyo Medical and Dental University, Tokyo, Japan. Electronic address: jun_sumino@ybb.ne.jp.
authors.forename: Jun
authors.initials: J
authors.lastname: Sumino
authors.affiliation: Department of Computational Biology, Graduate School of Biomedical Science, Tokyo Medical and Dental University, Tokyo, Japan. Electronic address: tanaka@bioinfo.tmd.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Maxillofacial Surgery, Maxillofacial Reconstruction and Function, Division of Maxillofacial and Neck Reconstruction, Tokyo Medical and Dental University, Tokyo, Japan. Electronic address: haradak.mfs@tmd.ac.jp.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Harada
mesh_terms: D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D017931:DNA Primers; D006358:Hot Temperature; D006801:Humans; D009062:Mouth Neoplasms / Q000235:genetics / Q000473:pathology*; D010641:Phenotype; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000235:genetics / Q000502:physiology*
chemical_list: D014408:Biomarkers, Tumor; D017931:DNA Primers; C474013:HTRA3 protein, human; D012697:Serine Endopeptidases
keywords: Carcinogenesis; HtrA3; Laser microdissection; Microarray; Oral; Squamous cell carcinoma