title: Methylated cyclin D2 gene circulating in the blood as a prognosis predictor of hepatocellular carcinoma.
abstract: BACKGROUND
  Prognosis of hepatocellular carcinoma (HCC) remains poor because of high recurrence rate. We examined preoperatively the methylated CCND2 gene levels present in the serum following release from HCC cells as a prognosis predictor in patients undergoing curative hepatectomy.
  
  
  METHODS
  Quantitative real-time RT-PCR and quantitative methylation-specific PCR were used to measure methylated CCND2 gene and its mRNA levels.
  
  
  RESULTS
  The CCND2 mRNA levels were down-regulated in HCC with early intrahepatic recurrence (IHR) within 1year of curative hepatectomy. We also identified that this down-regulation was due to promoter hypermethylation. In 70 HCC patients who underwent curative hepatectomy, 39 patients sero-positive for the methylated CCND2 gene (>70pg/ml serum) exhibited a significantly shorter disease-free survival (DFS) period (P=0.02) than the 31 patients who were sero-negative for the methylated CCND2 gene. None of the sero-negative patients demonstrated early IHR, and this method of serum testing did not produce any false-negative predictions for early IHR. Multivariate analysis showed that the serum level of methylated CCND2 was an independent risk factor for DFS (hazard ratio of 1.866, 95% CI: 1.106-3.149).
  
  
  CONCLUSIONS
  Methylated CCND2 gene in the serum serves as a prognosis predictor of HCC after curative hepatectomy.
authors.affiliation: Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Tsutsui
authors.forename: Norio
authors.initials: N
authors.lastname: Iizuka
authors.forename: Toyoki
authors.initials: T
authors.lastname: Moribe
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Miura
authors.forename: Naoki
authors.initials: N
authors.lastname: Kimura
authors.forename: Shigeru
authors.initials: S
authors.lastname: Tamatsukuri
authors.forename: Hideo
authors.initials: H
authors.lastname: Ishitsuka
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Fujita
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hamamoto
authors.forename: Ryouichi
authors.initials: R
authors.lastname: Tsunedomi
authors.forename: Michihisa
authors.initials: M
authors.lastname: Iida
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Tokuhisa
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Takao
authors.initials: T
authors.lastname: Tamesa
authors.forename: Isao
authors.initials: I
authors.lastname: Sakaida
authors.forename: Masaaki
authors.initials: M
authors.lastname: Oka
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics; D056742:Cyclin D2 / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D008745:Methylation; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012333:RNA, Messenger / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D056742:Cyclin D2; D012333:RNA, Messenger