{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T03:58:38Z","timestamp":1771905518566,"version":"3.50.1"},"reference-count":31,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2023,10,28]],"date-time":"2023-10-28T00:00:00Z","timestamp":1698451200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"AGAUR","award":["2022_FI_B00528"],"award-info":[{"award-number":["2022_FI_B00528"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/cancers15215182","type":"journal-article","created":{"date-parts":[[2023,10,29]],"date-time":"2023-10-29T05:01:08Z","timestamp":1698555668000},"page":"5182","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Characterisation of Aberrant Metabolic Pathways in Hepatoblastoma Using Liquid Chromatography and Tandem Mass Spectrometry (LC-MS\/MS)"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3383-738X","authenticated-orcid":false,"given":"Alison","family":"Whitby","sequence":"first","affiliation":[{"name":"Children\u2019s Brain Tumour Research Centre, School of Medicine, Biodiscovery Institute, University of Nottingham, Nottingham NG7 2RD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pardeep","family":"Pabla","sequence":"additional","affiliation":[{"name":"School of Medicine, Royal Derby Hospital Centre, University of Nottingham, Derby DE22 3DT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bhoomi","family":"Shastri","sequence":"additional","affiliation":[{"name":"Children\u2019s Brain Tumour Research Centre, School of Medicine, Biodiscovery Institute, University of Nottingham, Nottingham NG7 2RD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laudina","family":"Amugi","sequence":"additional","affiliation":[{"name":"Centre for Analytical Bioscience, Advanced Materials and Healthcare Division, School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, UK"},{"name":"Phenome Centre Birmingham, School of Biosciences, University of Birmingham, Birmingham, B15 2TT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00c1lvaro","family":"Del R\u00edo-\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Childhood Liver Oncology Group, Translational Program in Cancer Research (CARE), Germans Trias i Pujol Research Institute (IGTP), 08916 Badalona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red (CIBER) en Enfermedades Hep\u00e1ticas y Digestivas, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3689-2130","authenticated-orcid":false,"given":"Dong-Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Centre for Analytical Bioscience, Advanced Materials and Healthcare Division, School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Royo","sequence":"additional","affiliation":[{"name":"Childhood Liver Oncology Group, Translational Program in Cancer Research (CARE), Germans Trias i Pujol Research Institute (IGTP), 08916 Badalona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4690-4027","authenticated-orcid":false,"given":"Carolina","family":"Armengol","sequence":"additional","affiliation":[{"name":"Childhood Liver Oncology Group, Translational Program in Cancer Research (CARE), Germans Trias i Pujol Research Institute (IGTP), 08916 Badalona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red (CIBER) en Enfermedades Hep\u00e1ticas y Digestivas, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8444-6007","authenticated-orcid":false,"given":"Madhumita","family":"Dandapani","sequence":"additional","affiliation":[{"name":"Children\u2019s Brain Tumour Research Centre, School of Medicine, Biodiscovery Institute, University of Nottingham, Nottingham NG7 2RD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s40880-019-0411-7","article-title":"Incidence trends and survival prediction of hepatoblastoma in children: A population-based study","volume":"39","author":"Feng","year":"2019","journal-title":"Cancer Commun."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e29763","DOI":"10.1002\/pbc.29763","article-title":"Incidence and 5-year survival of children and adolescents with hepatoblastoma in the United States","volume":"69","author":"Kahla","year":"2022","journal-title":"Pediatr. 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