Research Papers:

Determination of candidate metabolite biomarkers associated with recurrence of HCV-related hepatocellular carcinoma

Zhicheng Liu, Pierre Nahon, Zaifang Li, Peiyuan Yin, Yanli Li, Roland Amathieu, Nathalie Ganne-Carrié, Marianne Ziol, Nicolas Sellier, Olivier Seror, Laurence Le Moyec, Philippe Savarin _ and Guowang Xu

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Oncotarget. 2018; 9:6245-6258. https://doi.org/10.18632/oncotarget.23500

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Zhicheng Liu1,2, Pierre Nahon3,4,10, Zaifang Li1, Peiyuan Yin1, Yanli Li1, Roland Amathieu2,5, Nathalie Ganne-Carrié3,10, Marianne Ziol6,7, Nicolas Sellier8, Olivier Seror4,8, Laurence Le Moyec9, Philippe Savarin2,* and Guowang Xu1,*

1CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China

2Université Paris 13, Sorbonne Paris Cité, Laboratoire de Chimie, Structures et Propriétés de Biomateriaux et d’Agents Therapeutiques, UMR 7244, Bobigny, France

3Hepatology Unit, Jean Verdier Teaching Hospital, AP-HP, Bondy, France

4INSERM U1162, Génomique Fonctionnelle des Tumeurs Solides, INSERM U1162, Paris, France

5Intensive Care Unit, Jean Verdier Teaching Hospital, AP-HP, Bondy, France

6APHP, Service d'Anatomie Pathologique, Hôpital Jean Verdier, BB-0033-00027, Centre de Ressources Biologiques Maladies du foie, Groupe Hospitalier, Paris-Seine-Saint-Denis, France

7BB-0033-00027, Centre de Ressources Biologiques Maladies du Foie, Groupe Hospitalier Paris-Seine-Saint-Denis, Bondy, France

8APHP, Service de Radiologie, Hôpital Jean Verdier, Bondy, France

9Université d’Evry Val d’Essonne, UBIAE, EA7362, Evry, France

10University Paris 13, Bobigny, France

*These authors contributed equally to this work

Correspondence to:

Philippe Savarin, email: [email protected]

Guowang Xu, email: [email protected]

Keywords: HCV-related HCC, recurrence, GC-MS, metabolomics, metabolic biomarker

Received: August 06, 2017     Accepted: October 05, 2017     Published: December 15, 2017


Hepatitis C virus (HCV) infection is associated with a high risk of developing hepatocellular carcinoma (HCC) and HCC recurrence remains the primary threat to outcomes after curative therapy. In this study, we compared recurrent and non-recurrent HCC patients treated with radiofrequency ablation (RFA) in order to identify characteristic metabolic profile variations associated with HCC recurrence. Gas chromatography-mass spectrometry (GC-MS) -based metabolomic analyses were conducted on serum samples obtained before and after RFA therapy. Significant variations were observed in metabolites in the glycerolipid, tricarboxylic acid (TCA) cycle, fatty acid, and amino acid pathways between recurrent and non-recurrent patients. Observed differences in metabolites associated with recurrence did not coincide before and after treatment except for fatty acids. Based on the comparison of serum metabolomes between recurrent and non-recurrent patients, key discriminatory metabolites were defined by a random forest (RF) test. Two combinations of these metabolites before and after RFA treatment showed outstanding performance in predicting HCV-related HCC recurrence, they were further confirmed by an external validation set. Our study showed that the determined combination of metabolites may be potential biomarkers for the prediction of HCC recurrence before and after RFA treatment.

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