دورية أكاديمية
Characterisation of Aberrant Metabolic Pathways in Hepatoblastoma Using Liquid Chromatography and Tandem Mass Spectrometry (LC-MS/MS)
| العنوان: | Characterisation of Aberrant Metabolic Pathways in Hepatoblastoma Using Liquid Chromatography and Tandem Mass Spectrometry (LC-MS/MS) |
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| المؤلفون: | Whitby, Alison, Pabla, Pardeep, Shastri, Bhoomi, Amugi, Laudina, Del Río-Álvarez, Álvaro, Kim, Dong-Hyun, Royo, Laura, Armengol, Carolina, Dandapani, Madhumita |
| بيانات النشر: | MDPI |
| سنة النشر: | 2023 |
| المجموعة: | University of Nottingham: Repository@Nottingham |
| مصطلحات موضوعية: | hepatoblastoma, liquid chromatography and tandem mass spectrometry, metabolomics, acylcarnitine, fatty acid oxidation, carnitine palmitoyl transferase (CPT1) |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| العلاقة: | https://nottingham-repository.worktribe.com/output/26811159Test; Cancers; Volume 15; Issue 21; https://nottingham-repository.worktribe.com/file/26811159/1/Characterisation%20of%20Aberrant%20Metabolic%20Pathways%20in%20Hepatoblastoma%20Using%20Liquid%20Chromatography%20and%20Tandem%20Mass%20Spectrometry%20%28LC-MS%2FMS%29Test |
| DOI: | 10.3390/cancers15215182 |
| الإتاحة: | https://doi.org/10.3390/cancers15215182Test https://nottingham-repository.worktribe.com/file/26811159/1/Characterisation%20of%20Aberrant%20Metabolic%20Pathways%20in%20Hepatoblastoma%20Using%20Liquid%20Chromatography%20and%20Tandem%20Mass%20Spectrometry%20%28LC-MS%2FMS%29Test https://nottingham-repository.worktribe.com/output/26811159Test |
| حقوق: | openAccess ; https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.4AD2AA60 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3390/cancers15215182 |
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