title: Reduced Expression of Adherens Junctions Associated Protein 1 Predicts Recurrence of Hepatocellular Carcinoma After Curative Hepatectomy.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC) frequently recurs after curative resection. Therefore, the availability of sensitive biomarkers for progression and recurrence is essential for managing patients' clinical course. Adherens junctions associated protein 1 (AJAP1) may serve this purpose, because it mediates activities of tumor cells.
  
  
  METHODS
  AJAP1 mRNA levels and those of genes encoding potential interacting proteins, such as SRC in HCC cell lines, and 144 pairs of resected liver tissues were determined as well as the methylation status of the AJAP1 promoter and copy number changes at AJAP1 locus. The expression pattern of AJAP1 protein was evaluated using immunohistochemistry.
  
  
  RESULTS
  AJAP1 mRNA levels varied among nine HCC cell lines, and AJAP1 expression was reactivated after demethylation of its promoter. AJAP1 mRNA levels correlated inversely with those of SRC in HCC cell lines and tissues. AJAP1 mRNA levels were suppressed in HCC tissues. The expression pattern of AJAP1 correlated significantly with that of AJAP1 mRNA. Low levels of AJAP1 mRNA in patients with HCC associated significantly with elevated levels of tumor markers, larger tumor size, serosal infiltration, vascular invasion, hypermethylation of the AJAP1 promoter, and copy number loss at AJAP1 locus. Patients with low levels of AJAP1 expression were more likely to experience shorter disease-free survival (DFS), and multivariate analysis identified low AJAP1 expression as an independent factor for predicting DFS.
  
  
  CONCLUSIONS
  AJAP1 may function as a key regulatory molecule associated with the recurrence of HCC. Hypermethylation of the AJAP1 promoter is a key regulatory mechanism controlling AJAP1 expression.
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ezaka
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan. m-kanda@med.nagoya-u.ac.jp.
authors.forename: Mitsuro
authors.initials: M
authors.lastname: Kanda
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sugimoto
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Shimizu
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Hisaharu
authors.initials: H
authors.lastname: Oya
authors.affiliation: Department of Surgery, Aichi-Gakuin University School of Dentistry, Nagoya, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Nomoto
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sueoka
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Takami
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Hashimoto
authors.affiliation: Department of Hepato-biliary-pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Yukiyasu
authors.initials: Y
authors.lastname: Okamura
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Suguru
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Fujii
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Goro
authors.initials: G
authors.lastname: Nakayama
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Koike
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Michitaka
authors.initials: M
authors.lastname: Fujiwara
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kodera
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology / Q000601:surgery*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006498:Hepatectomy / Q000009:adverse effects*; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D009367:Neoplasm Staging; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
chemical_list: C483313:AJAP1 protein, human; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D012333:RNA, Messenger