Identification of a bona fide microRNA biomarker in serum exosomes that predicts hepatocellular carcinoma recurrence after liver transplantation

K. Sugimachi, T. Matsumura, H. Hirata, R. Uchi, M. Ueda, H. Ueo, Y. Shinden, T. Iguchi, H. Eguchi, K. Shirabe, T. Ochiya, Y. Maehara, K. Mimori

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Abstract

BackgroundPredictive 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.MethodsWe 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.ResultsWe 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.ConclusionCirculating miRs in serum exosomes have potential as novel biomarkers for predicting HCC recurrence.

Original languageEnglish
Pages (from-to)532-538
Number of pages7
JournalBritish journal of cancer
Volume112
Issue number3
DOIs
Publication statusPublished - Feb 3 2015

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Exosomes
MicroRNAs
Liver Transplantation
Hepatocellular Carcinoma
Biomarkers
Recurrence
Serum
Genes
Up-Regulation

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Identification of a bona fide microRNA biomarker in serum exosomes that predicts hepatocellular carcinoma recurrence after liver transplantation. / Sugimachi, K.; Matsumura, T.; Hirata, H.; Uchi, R.; Ueda, M.; Ueo, H.; Shinden, Y.; Iguchi, T.; Eguchi, H.; Shirabe, K.; Ochiya, T.; Maehara, Y.; Mimori, K.

In: British journal of cancer, Vol. 112, No. 3, 03.02.2015, p. 532-538.

Research output: Contribution to journalArticle

Sugimachi, K, Matsumura, T, Hirata, H, Uchi, R, Ueda, M, Ueo, H, Shinden, Y, Iguchi, T, Eguchi, H, Shirabe, K, Ochiya, T, Maehara, Y & Mimori, K 2015, 'Identification of a bona fide microRNA biomarker in serum exosomes that predicts hepatocellular carcinoma recurrence after liver transplantation', British journal of cancer, vol. 112, no. 3, pp. 532-538. https://doi.org/10.1038/bjc.2014.621
Sugimachi, K. ; Matsumura, T. ; Hirata, H. ; Uchi, R. ; Ueda, M. ; Ueo, H. ; Shinden, Y. ; Iguchi, T. ; Eguchi, H. ; Shirabe, K. ; Ochiya, T. ; Maehara, Y. ; Mimori, K. / Identification of a bona fide microRNA biomarker in serum exosomes that predicts hepatocellular carcinoma recurrence after liver transplantation. In: British journal of cancer. 2015 ; Vol. 112, No. 3. pp. 532-538.
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N2 - BackgroundPredictive 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.MethodsWe 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.ResultsWe 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.ConclusionCirculating miRs in serum exosomes have potential as novel biomarkers for predicting HCC recurrence.

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