Liu Zhicheng, Nahon Pierre, Li Zaifang, Yin Peiyuan, Li Yanli, Amathieu Roland, Ganne-Carrié Nathalie, Ziol Marianne, Sellier Nicolas, Seror Olivier, Le Moyec Laurence, Savarin Philippe, Xu Guowang
CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
Université Paris 13, Sorbonne Paris Cité, Laboratoire de Chimie, Structures et Propriétés de Biomateriaux et d'Agents Therapeutiques, UMR 7244, Bobigny, France.
Oncotarget. 2017 Dec 15;9(5):6245-6258. doi: 10.18632/oncotarget.23500. eCollection 2018 Jan 19.
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.
丙型肝炎病毒（HCV）感染与肝细胞癌（HCC）的高发病风险相关，且HCC复发仍是根治性治疗后影响预后的主要威胁。在本研究中，我们比较了接受射频消融（RFA）治疗的复发性和非复发性HCC患者，以确定与HCC复发相关的特征性代谢谱变化。对RFA治疗前后采集的血清样本进行了基于气相色谱-质谱联用（GC-MS）的代谢组学分析。复发性和非复发性患者在甘油脂质、三羧酸（TCA）循环、脂肪酸和氨基酸途径中的代谢物存在显著差异。除脂肪酸外，复发相关代谢物在治疗前后观察到的差异并不一致。基于复发性和非复发性患者血清代谢组的比较，通过随机森林（RF）检验确定了关键的鉴别代谢物。RFA治疗前后这些代谢物的两种组合在预测HCV相关HCC复发方面表现出色，并通过外部验证集进一步得到证实。我们的研究表明，所确定的代谢物组合可能是预测RFA治疗前后HCC复发的潜在生物标志物。
