Hepatoblastoma (HB) is a rare childhood tumour with an evolving molecular landscape. We present the first comprehensive metabolomic analysis using untargeted and targeted liquid chromatography coupled to high-resolution tandem mass spectrometry (LC-MS/MS) of paired tumour and non-tumour surgical samples in HB patients (n= 8 pairs). This study demonstrates that the metabolomic landscape of HB is distinct from that of non-tumour (NT) liver tissue, with 35 differentially abundant metabolites mapping onto pathways such as fatty acid transport, glycolysis, the tricarboxylic acid (TCA) cycle, branched-chain amino acid degradation and glutathione synthesis. Targeted metabolomics demonstrated reduced short-chain acylcarnitines and a relative accumulation of branched-chain amino acids. Medium- and long-chain acylcarnitines in HB were similar to those in NT. The metabolomic changes reported are consistent with previously reported transcriptomic data from tumour and non-tumour samples (49 out of 54 targets) as well as metabolomic data obtained using other techniques. Gene set enrichment analysis (GSEA) from RNAseq data (n= 32 paired HB and NT samples) demonstrated a downregulation of the carnitine metabolome and immunohistochemistry showed a reduction in CPT1a (n= 15 pairs), which transports fatty acids into the mitochondria, suggesting a lack of utilisation of long-chain fatty acids in HB. Thus, our findings suggest a reduced metabolic flux in HB which is corroborated at the gene expression and protein levels. Further work could yield novel insights and new therapeutic targets.
肝母细胞瘤是一种罕见的儿童肿瘤，其分子特征处于动态演变中。本研究首次采用非靶向与靶向液相色谱-高分辨率串联质谱联用技术，对肝母细胞瘤患者的配对肿瘤与非肿瘤手术样本（n=8对）进行了全面代谢组学分析。研究显示肝母细胞瘤的代谢特征与非肿瘤肝组织存在显著差异，共鉴定出35种差异丰度代谢物，主要富集于脂肪酸转运、糖酵解、三羧酸循环、支链氨基酸降解及谷胱甘肽合成等通路。靶向代谢组学分析显示短链酰基肉碱水平降低，支链氨基酸相对积累，而中长链酰基肉碱水平在肿瘤与非肿瘤组织间无显著差异。这些代谢变化与既往报道的肿瘤/非肿瘤样本转录组数据（54个靶点中49个相符）及其他技术获得的代谢组学结果具有一致性。基于RNA测序数据的基因集富集分析（n=32对样本）显示肉碱代谢组下调，免疫组化实验（n=15对）证实线粒体脂肪酸转运蛋白CPT1a表达降低，提示肝母细胞瘤中存在长链脂肪酸利用障碍。因此，本研究从基因表达和蛋白水平证实了肝母细胞瘤代谢通量的降低，相关发现可为探索新型治疗靶点提供重要依据。
肿瘤(癌症)患者之家