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