A Pilot Study on the Utility of Serum Metabolomics in Neuroblastoma Patients and Xenograft Models

Beaudry, Paul; Campbell, Martin; Dang, Ngoc Ha; Wen, Jing; Blote, Karen; Weljie, Aalim M.

doi:10.1002/pbc.25784

Cited by 10 publications

(8 citation statements)

References 29 publications

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“…In this paper, we show the application of a HRMS metabolomic approach to NB. Other authors have previously described metabolomics studies on NB using NMR (12) or LC-MS (13). Both papers confirmed the potential of metabolomic approaches applied to NB.…”

Section: Discussionmentioning

confidence: 59%

“…A key point of metabolomics is the development of robust workflows for compound identification, data analysis and biological interpretation (11). Previous metabolomic analyses conducted on murine xenograft models with nuclear magnetic resonance (NMR) (12) or plasma of NB patients by LC-MS (13) support the potential of metabolomic profiling for improving NB risk-group stratification and outcome prediction. Nevertheless, these studies were not able to provide candidate biomarkers with an independent validation in a second cohort of patients.…”

Section: Introductionmentioning

confidence: 99%

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Untargeted LC-HRMS Based-Plasma Metabolomics Reveals 3-O-Methyldopa as a New Biomarker of Poor Prognosis in High-Risk Neuroblastoma

et al. 2022

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Neuroblastoma (NB) is the most common extracranial malignant tumor in children. Although the survival rate of NB has improved over the years, the outcome of NB still remains poor for over 30% of cases. A more accurate risk stratification remains a key point in the study of NB and the availability of novel prognostic biomarkers of “high-risk” at diagnosis could help improving patient stratification and predicting outcome.In this paper we show a biomarker discovery approach applied to the plasma of 172 NB patients. Plasma samples from a first cohort of NB patients and age-matched healthy controls were used for untargeted metabolomics analysis based on high-resolution mass spectrometry (HRMS). Differential expression analysis highlighted a number of metabolites annotated with a high degree of identification. Among them, 3-O-methyldopa (3-O-MD) was validated in a second cohort of NB patients using a targeted metabolite profiling approach and its prognostic potential was also analyzed by survival analysis on patients with 3 years follow-up. High expression of 3-O-MD was associated with worse prognosis in the subset of patients with stage M tumor (log-rank p < 0.05) and, among them, it was confirmed as a prognostic factor able to stratify high-risk patients older than 18 months. 3-O-MD might be thus considered as a novel prognostic biomarker of NB eligible to be included at diagnosis among catecholamine metabolite panels in prospective clinical studies. Further studies are warranted to exploit other potential biomarkers highlighted using our approach.

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Section: Discussionmentioning

confidence: 59%

Section: Introductionmentioning

confidence: 99%

Untargeted LC-HRMS Based-Plasma Metabolomics Reveals 3-O-Methyldopa as a New Biomarker of Poor Prognosis in High-Risk Neuroblastoma

et al. 2022

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“…More precisely, they defined the so-called metabolic fingerprint of neuroblastoma as a metabolic marker to control the disease course. Another valuable approach includes metabolome analysis of patients’ sera to improve the reliability of diagnosis or risk-stratification of neuroblastoma patients, as reported by Beaudry et al [ 133 ]. The authors performed a retrospective metabolome study, examining whether the patient’s sera discriminate low from HR neuroblastoma patients.…”

Section: Current Views and Directions In Neuroblastoma Therapy: The Omentioning

confidence: 99%

Neuroblastoma treatment in the post-genomic era

et al. 2017

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Neuroblastoma is an embryonic malignancy of early childhood originating from neural crest cells and showing heterogeneous biological, morphological, genetic and clinical characteristics. The correct stratification of neuroblastoma patients within risk groups (low, intermediate, high and ultra-high) is critical for the adequate treatment of the patients.High-throughput technologies in the Omics disciplines are leading to significant insights into the molecular pathogenesis of neuroblastoma. Nonetheless, further study of Omics data is necessary to better characterise neuroblastoma tumour biology. In the present review, we report an update of compounds that are used in preclinical tests and/or in Phase I-II trials for neuroblastoma. Furthermore, we recapitulate a number of compounds targeting proteins associated to neuroblastoma: MYCN (direct and indirect inhibitors) and downstream targets, Trk, ALK and its downstream signalling pathways. In particular, for the latter, given the frequency of ALK gene deregulation in neuroblastoma patients, we discuss on second-generation ALK inhibitors in preclinical or clinical phases developed for the treatment of neuroblastoma patients resistant to crizotinib.We summarise how Omics drive clinical trials for neuroblastoma treatment and how much the research of biological targets is useful for personalised medicine. Finally, we give an overview of the most recent druggable targets selected by Omics investigation and discuss how the Omics results can provide us additional advantages for overcoming tumour drug resistance.

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“…Surprisingly, to our knowledge, little is known about metabolic pro les of tissues from diverse murine strains including NSG. Only one study described tissue metabolomes from two naïve male C57BL/6 29 , and several works showed tissue metabolic rewiring 13,30,31 and plasma metabolomes 13,32 .…”

Section: Introductionmentioning

confidence: 99%

In vivo metabolomic study uncovers distinct metabolic phenotypes of host tissues and predicts oxidative state of acute myeloid leukemia

Cognet

Stuani

Farge

et al. 2021

Preprint

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Background Metabolic adaptation is a hallmark of cancer including acute myeloid leukemia (AML). Tumor microenvironment is also described as an essential support of leukemic metabolism. We explored how systemic and tissue metabolism was rewired in leukemia-bearing mice and upon chemotherapy. Methods Using AML cell line- and primary patient-derived xenograft models, we developed in vivo metabolomics to uncover the metabolic pattern of 10 tissues including plasma, bone marrow, spleen, liver, adipose tissue, lung, pancreas, kidney, heart and muscle. Results In vivo targeted mass spectrometry allowed metabolic characterization of tissues from naïve and AML-xenografted immunocompromised mice. AML xenotransplantation and cytarabine treatment induced AML cell type-dependent global changes in tissue metabolomes. Infiltration of high OxPHOS MOLM14 cells that are intrinsically chemoresistant, induced minor changes in tissue metabolomes. In contrast, low OxPHOS U937 xenograft led to major reprogramming of metabolic tissue niches for survival upon chemotherapy. Interestingly, plasma metabolite signatures could predict the oxidative phenotype of leukemic cells. Conclusion Major metabolic changes in host tissues play a crucial role in tumor xenotransplantation and define their OxPHOS state in AML. Since mitochondrial phenotype is an essential determinant of drug response in AML, plasma metabolite signatures might be novel biomarkers for patient stratification.

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A Pilot Study on the Utility of Serum Metabolomics in Neuroblastoma Patients and Xenograft Models

Abstract: Serum metabolomic analysis can distinguish several characteristics of NB. A larger analysis of COG banked sera is warranted.

Cited by 10 publications

References 29 publications

Untargeted LC-HRMS Based-Plasma Metabolomics Reveals 3-O-Methyldopa as a New Biomarker of Poor Prognosis in High-Risk Neuroblastoma

Untargeted LC-HRMS Based-Plasma Metabolomics Reveals 3-O-Methyldopa as a New Biomarker of Poor Prognosis in High-Risk Neuroblastoma

Neuroblastoma treatment in the post-genomic era

In vivo metabolomic study uncovers distinct metabolic phenotypes of host tissues and predicts oxidative state of acute myeloid leukemia

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