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Enhanced glycolysis, glutaminolysis, and fatty acid synthesis have been implicated in hepatoblastoma cell proliferation and survival. In this study, we screened for altered overexpression of metabolic enzymes in hepatoblastoma tumors at tissue and single-cell levels, establishing and validating a hepatoblastoma tumor expression metabolic score using machine learning. Starting from the Mammalian Metabolic Enzyme Database, bulk RNA sequencing data from GSE104766 and GSE131329 datasets were analyzed using supervised methods to compare tumors versus adjacent liver tissue. Differential expression analysis identified 287 significantly regulated enzymes, 59 of which were overexpressed in tumors. Functional enrichment in the KEGG metabolic database highlighted a network enriched in amino acid metabolism, as well as carbohydrate, steroid, one-carbon, purine, and glycosaminoglycan metabolism pathways. A metabolic score based on these enzymes was validated in an independent cohort (GSE131329) and applied to single-cell transcriptomic data (GSE180665), predicting tumor cell status with an AUC of 0.98 (sensitivity 0.93, specificity 0.94). Elasticnet model tuning on individual marker expression revealed top tumor predictive markers, including FKBP10, ATP1A2, NT5DC2, UGT3A2, PYCR1, CKB, GPX7, DNMT3B, GSTP1, and OXCT1. These findings indicate that an activated metabolic transcriptional program, potentially influencing epigenetic functions, is observed in hepatoblastoma tumors and confirmed at the single-cell level.<\/jats:p>","DOI":"10.3390\/ijms252313044","type":"journal-article","created":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T10:07:10Z","timestamp":1733306830000},"page":"13044","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Characterization of an Activated Metabolic Transcriptional Program in Hepatoblastoma Tumor Cells Using scRNA-seq"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1215-5857","authenticated-orcid":false,"given":"Claudia","family":"Monge","sequence":"first","affiliation":[{"name":"Unit\u00e9 Organisation Nucl\u00e9aire et Oncogen\u00e8se, INSERM U993, Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1428-4852","authenticated-orcid":false,"given":"Raquel","family":"Franc\u00e9s","sequence":"additional","affiliation":[{"name":"Energy & Memory, Brain Plasticity Unit, CNRS, ESPCI Paris, PSL Research University, 75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6541-5395","authenticated-orcid":false,"given":"Agn\u00e8s","family":"Marchio","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Organisation Nucl\u00e9aire et Oncogen\u00e8se, INSERM U993, Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9407-1592","authenticated-orcid":false,"given":"Pascal","family":"Pineau","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Organisation Nucl\u00e9aire et Oncogen\u00e8se, INSERM U993, Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Desterke","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine du Kremlin Bic\u00eatre, University Paris-Sud, Universit\u00e9 Paris-Saclay, 94270 Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5726-8814","authenticated-orcid":false,"given":"Jorge","family":"Mata-Garrido","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Organisation Nucl\u00e9aire et Oncogen\u00e8se, INSERM U993, Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1002\/pbc.24215","article-title":"The Epidemiology of Hepatoblastoma","volume":"59","author":"Spector","year":"2012","journal-title":"Pediatr. 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