ArticleOncogene2022
Identification of the ultrahigh-risk subgroup in neuroblastoma cases through DNA methylation analysis and its treatment exploiting cancer metabolism.
Article in Oncogene, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 14 citations in OpenAlex.
- Adult-onset neuroblastic tumor: An extremely rare entity in the adult population.Radiology case reports · 2026Article
- MYCN-driven metabolic remodelling of the tumour microenvironment in neuroblastoma: implications for stromal biology and CAF heterogeneity.Cancer metastasis reviews · 2026Review
- PHGDH at the crossroads: metabolic plasticity, metastatic paradoxes, and therapeutic reconnaissance in cancer.Journal of biomedical science · 2026Review
- Advances in multi-omics research on neuroblastoma.Frontiers in pediatrics · 2026Review
- Arginine depletion potentiates standard-of-care chemo-immunotherapy in preclinical models of high-risk neuroblastoma.Journal of experimental & clinical cancer research : CR · 2025Article
- Emerging Trends in Neuroblastoma Diagnosis, Therapeutics, and Research.Molecular neurobiology · 2025Review
- Article
- Prediction of Composite Clinical Outcomes for Childhood Neuroblastoma Using Multi-Omics Data and Machine Learning.International journal of molecular sciences · 2024Article
- Fine construction of gene coexpression network analysis using GTOM and RECODE detected a critical module of neuroblastoma stages 4 and 4S.Hereditas · 2024Article
- Review
- Article
- Integrative analysis with machine learning identifies diagnostic and prognostic signatures in neuroblastoma based on differentially DNA methylated enhancers between INSS stage 4 and 4S neuroblastoma.Journal of cancer research and clinical oncology · 2024Article
- Construction of methylation driver gene-related prognostic signature and development of a new prognostic stratification strategy in neuroblastoma.Genes & genomics · 2024Article
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Authors and funding
25 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuroblastomas require novel therapies that are based on the exploitation of their biological mechanism. To address this need, we analyzed the DNA methylation and expression datasets of neuroblastomas, extracted a candidate gene characterizing the aggressive features, and conducted functional studies. Based on the DNA methylation data, we identified a subgroup of neuroblastoma cases with 11q loss of heterozygosity with extremely poor prognosis. PHGDH, a serine metabolism-related gene, was extracted as a candidate with strong expression and characteristic methylation in this subgroup as well as in cases with MYCN amplification. PHGDH inhibition suppressed neuroblastoma cell proliferation in vitro and in vivo, indicating that the inhibition of serine metabolism by PHGDH inhibitors is a therapeutic alternative for neuroblastoma. Inhibiting the arginine metabolism, which is closely related to serine metabolism using arginine deiminase, had a combination effect both in vitro and in vivo, especially on extracellular arginine-dependent neuroblastoma cells with ASS1 deficiency. Expression and metabolome analyses of post-dose cells confirmed the synergistic effects of treatments targeting serine and arginine indicated that xCT inhibitors that inhibit cystine uptake could be candidates for further combinatorial treatment. Our results highlight the rational therapeutic strategy of targeting serine/arginine metabolism for intractable neuroblastoma.
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