title: Specific miRNA expression profiles of non-tumor liver tissue predict a risk for recurrence of hepatocellular carcinoma.
abstract: OBJECTIVE
  It is reasonable to investigate non-tumor liver tissues to predict a risk for development of hepatocellular carcinoma (HCC). A molecular analysis of chronically damaged liver tissues may identify specific miRNA expression profiles associated with a risk for multicentric (MC) HCC.
  
  
  METHODS
  Twenty HCC patients, who underwent a curative hepatectomy were classified into two groups: a non-MC group (no MC recurrence in more than 3 years, n = 10) and an MC group (MC recurrence within 3 years after hepatectomy, n = 10). An miRNA microarray (955 probes) was used to compare the miRNA expression patterns of the non-cancerous liver tissues between the two groups. This study identified the differentially expressed miRNA related to MC recurrence in the liver remnant.
  
  
  RESULTS
  No differences were observed between the two groups in the liver function tests and pathological variables including both tumor factors and non-tumor liver tissues. The investigation selected 20 differentially expressed miRNA related to MC recurrence. Eighteen miRNA were downregulated, while two miRNA were upregulated in the MC group. A hierarchical clustering analysis identified a cluster that may be associated with risk of the MC recurrence of HCC. The MC recurrence-related miRNA included let-7d*, miR-328 and miR18a*, which potentially regulate K-ras gene expression. A significant inverse correlation between the miR-18a* expression and the K-ras mRNA expression was confirmed by quantitative reverse transcription polymerase chain reaction.
  
  
  CONCLUSIONS
  Specific miRNA expression signatures in non-cancerous liver tissue may help to predict the risk for de novo development of HCC.
authors.affiliation: Department of Surgery, The University of Tokushima, Tokushima, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Utsunomiya
authors.forename: Daichi
authors.initials: D
authors.lastname: Ishikawa
authors.forename: Michihito
authors.initials: M
authors.lastname: Asanoma
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Yamada
authors.forename: Shuichi
authors.initials: S
authors.lastname: Iwahashi
authors.forename: Mami
authors.initials: M
authors.lastname: Kanamoto
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Arakawa
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ikemoto
authors.forename: Yuji
authors.initials: Y
authors.lastname: Morine
authors.forename: Satoru
authors.initials: S
authors.lastname: Imura
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ishibashi
authors.forename: Chie
authors.initials: C
authors.lastname: Takasu
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Shimada
keywords: hepatocellular carcinoma; miRNA microarray; multicentric occurrence; non-tumor tissue; recurrence