{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T07:55:27Z","timestamp":1781769327071,"version":"3.54.5"},"reference-count":29,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"abstract":"<jats:p>Despite its clinical importance, the metabolic landscape of MYCN nonamplified neuroblastoma (MYCN\u2010NA NB) remains poorly defined. In this study, we performed integrated metabolic characterization of 22 NB samples by combining single\u2010cell RNA sequencing (scRNA\u2010seq) with proteomics and metabolomics. This was followed by multi\u2010omics integration, two\u2010way orthogonal partial least squares analysis, and biomarker selection using a random forest classifier. The scRNA\u2010seq analysis of NB tumors revealed that, compared to the MYCN\u2010amplified (MYCN\u2010A) group, the MYCN\u2010NA group exhibited higher proportions of T\u00a0cells, monocytes, and neurons, while lipid metabolism pathways were specifically enriched. Proteomics identified 821 differentially expressed proteins [27 upregulated and 794 downregulated in the high\u2010risk (HR) NB group], and functional analysis indicated that these proteins were primarily involved in biological processes such as the tricarboxylic acid cycle (TCA) and lipid metabolism. Metabolomics further detected 15 significantly altered metabolites associated with pathways such as linoleic acid metabolism. Integrated multiomics analysis identified key molecules, including RPL9 and POLR2G, with potentially critical roles in HR NB. Multi\u2010omics correlation and network analyses revealed significant interactions between key proteins (RPL9 and POLR2G) and metabolites (D\u2010ribose and 9\u2010oxoODE). The biomarker combination determined by random forest and bidirectional orthogonal partial least squares modeling underscored the central role of oxidative lipid metabolism remodeling in high\u2010risk disease progression. This study systematically elucidated the crucial role of lipid metabolic reprogramming in the pathogenesis of HR MYCN\u2010NA NB. These findings provide critical insight for uncovering the mechanisms underlying NB progression and for identifying potential therapeutic targets.<\/jats:p>","DOI":"10.1111\/febs.70595","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T07:35:12Z","timestamp":1781768112000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Deciphering the metabolic landscape of\n                    <scp>MYCN<\/scp>\n                    non\u2010amplified neuroblastoma through integrated multiomics"],"prefix":"10.1111","author":[{"given":"Lizhi","family":"Li","sequence":"first","affiliation":[{"name":"Fuzhou University Affiliated Provincial Hospital Fujian Provincial Hospital  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaobin","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Fujian Medical University Union Hospital Fujian Key Laboratory of Intelligent Imaging and Precision Radiotherapy for Tumors (Fujian Medical University), Clinical Research Center for Radiology and Radiotherapy of Fujian Province (Digestive, Hematological and Breast Malignancies)  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5728-1841","authenticated-orcid":false,"given":"Shan","family":"Liu","sequence":"additional","affiliation":[{"name":"Fujian Children's Hospital, College of Clinical Medicine for Obstetrics &amp; Gynecology and Pediatrics Fujian Medical University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2225-3100","authenticated-orcid":false,"given":"Zhihong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hematology Fuzhou University Affiliated Provincial Hospital, Fujian Provincial Hospital  China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"6423","DOI":"10.1007\/s12035-024-04680-w","article-title":"Emerging trends in Neuroblastoma diagnosis, therapeutics, and research","volume":"62","author":"Sharma R","year":"2025","journal-title":"Mol Neurobiol"},{"key":"e_1_2_10_3_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.neo.2025.101122","article-title":"Global, regional and national burden of neuroblastoma and other peripheral nervous system tumors, 1990 to 2021 and predictions to 2035: visualizing epidemiological characteristics based on GBD 2021","volume":"60","author":"Yue C","year":"2025","journal-title":"Neoplasia"},{"key":"e_1_2_10_4_1","doi-asserted-by":"crossref","first-page":"3229","DOI":"10.1200\/JCO.21.00278","article-title":"Revised Neuroblastoma risk classification system: a report from the Children's oncology 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