title: Identification of a bona fide microRNA biomarker in serum exosomes that predicts hepatocellular carcinoma recurrence after liver transplantation.
abstract: BACKGROUND
  Predictive biomarkers for the recurrence of hepatocellular carcinoma (HCC) have great benefit in the selection of treatment options, including liver transplantation (LT), for HCC. The purpose of this study was to identify specific microRNAs (miRs) in exosomes from the serum of patients with recurrent HCC and to validate these molecules as novel biomarkers for HCC recurrence.
  
  
  METHODS
  We employed microarray-based expression profiling of miRs derived from exosomes in the serum of HCC patients to identify a biomarker that distinguishes between patients with and without HCC recurrence after LT. This was followed by the validation in a separate cohort of 59 HCC patients who underwent living related LT. The functions and potential gene targets of the recurrence-specific miRs were analysed using a database, clinical samples and HCC cell lines.
  
  
  RESULTS
  We found that miR-718 showed significantly different expression in the serum exosomes of HCC cases with recurrence after LT compared with those without recurrence. Decreased expression of miR-718 was associated with HCC tumour aggressiveness in the validated cohort series. We identified HOXB8 as a potential target gene of miR-718, and its upregulation was associated with poor prognosis.
  
  
  CONCLUSIONS
  Circulating miRs in serum exosomes have potential as novel biomarkers for predicting HCC recurrence.
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu 874-0838, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Sugimachi
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu 874-0838, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Matsumura
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu 874-0838, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Hirata
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu 874-0838, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Uchi
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu 874-0838, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ueda
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu 874-0838, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ueo
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu 874-0838, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Shinden
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu 874-0838, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Iguchi
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu 874-0838, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Eguchi
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Shirabe
authors.affiliation: Group for Research of Molecular Functions and Targets, Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ochiya
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Maehara
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu 874-0838, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Mimori
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000473:pathology* / Q000601:surgery; D002478:Cells, Cultured; D055354:Exosomes; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood* / Q000473:pathology* / Q000601:surgery; D016031:Liver Transplantation; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D011379:Prognosis; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C490669:HOXB8 protein, human; D018398:Homeodomain Proteins; C000589574:MIRN718 microRNA, human; D035683:MicroRNAs