Untargeted LC-HRMS Based-Plasma Metabolomics Reveals 3-O-Methyldopa as a New Biomarker of Poor Prognosis in High-Risk Neuroblastoma
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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.845936/full |
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| author | Sebastiano Barco Chiara Lavarello Davide Cangelosi Martina Morini Alessandra Eva Luca Oneto Paolo Uva Gino Tripodi Alberto Garaventa Massimo Conte Andrea Petretto Giuliana Cangemi |
| author_facet | Sebastiano Barco Chiara Lavarello Davide Cangelosi Martina Morini Alessandra Eva Luca Oneto Paolo Uva Gino Tripodi Alberto Garaventa Massimo Conte Andrea Petretto Giuliana Cangemi |
| author_sort | Sebastiano Barco |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T07:42:14Z |
| format | Article |
| id | doaj.art-7a8128a33d5945b2aca2068cbc2d064d |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-12T07:42:14Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-7a8128a33d5945b2aca2068cbc2d064d2022-12-22T00:32:44ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-06-011210.3389/fonc.2022.845936845936Untargeted LC-HRMS Based-Plasma Metabolomics Reveals 3-O-Methyldopa as a New Biomarker of Poor Prognosis in High-Risk NeuroblastomaSebastiano Barco0Chiara Lavarello1Davide Cangelosi2Martina Morini3Alessandra Eva4Luca Oneto5Paolo Uva6Gino Tripodi7Alberto Garaventa8Massimo Conte9Andrea Petretto10Giuliana Cangemi11Chromatography and Mass Spectrometry Section, Central Laboratory of Analysis, IRCCS Istituto Giannina Gaslini, Genoa, ItalyCore Facilities Clinical Proteomics and Metabolomics, IRCCS Istituto Giannina Gaslini, Genoa, ItalyClinical Bioinformatics Unit, IRCCS Istituto Giannina Gaslini, Genoa, ItalyLaboratory of Molecular Biology, IRCCS Istituto Giannina Gaslini, Genoa, ItalyLaboratory of Molecular Biology, IRCCS Istituto Giannina Gaslini, Genoa, ItalyDIBRIS, University of Genoa, Genoa, ItalyClinical Bioinformatics Unit, IRCCS Istituto Giannina Gaslini, Genoa, ItalyChromatography and Mass Spectrometry Section, Central Laboratory of Analysis, IRCCS Istituto Giannina Gaslini, Genoa, ItalyDepartment of Pediatric Oncology and Hematology, IRCCS Istituto Giannina Gaslini, Genoa, ItalyDepartment of Pediatric Oncology and Hematology, IRCCS Istituto Giannina Gaslini, Genoa, ItalyCore Facilities Clinical Proteomics and Metabolomics, IRCCS Istituto Giannina Gaslini, Genoa, ItalyChromatography and Mass Spectrometry Section, Central Laboratory of Analysis, IRCCS Istituto Giannina Gaslini, Genoa, ItalyNeuroblastoma (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.https://www.frontiersin.org/articles/10.3389/fonc.2022.845936/fullneuroblastomametabolomicsbiomarkerhigh resolution mass spectrometrycatecholamines3-O-methyldopa |
| spellingShingle | Sebastiano Barco Chiara Lavarello Davide Cangelosi Martina Morini Alessandra Eva Luca Oneto Paolo Uva Gino Tripodi Alberto Garaventa Massimo Conte Andrea Petretto Giuliana Cangemi Untargeted LC-HRMS Based-Plasma Metabolomics Reveals 3-O-Methyldopa as a New Biomarker of Poor Prognosis in High-Risk Neuroblastoma Frontiers in Oncology neuroblastoma metabolomics biomarker high resolution mass spectrometry catecholamines 3-O-methyldopa |
| title | Untargeted LC-HRMS Based-Plasma Metabolomics Reveals 3-O-Methyldopa as a New Biomarker of Poor Prognosis in High-Risk Neuroblastoma |
| title_full | Untargeted LC-HRMS Based-Plasma Metabolomics Reveals 3-O-Methyldopa as a New Biomarker of Poor Prognosis in High-Risk Neuroblastoma |
| title_fullStr | Untargeted LC-HRMS Based-Plasma Metabolomics Reveals 3-O-Methyldopa as a New Biomarker of Poor Prognosis in High-Risk Neuroblastoma |
| title_full_unstemmed | Untargeted LC-HRMS Based-Plasma Metabolomics Reveals 3-O-Methyldopa as a New Biomarker of Poor Prognosis in High-Risk Neuroblastoma |
| title_short | Untargeted LC-HRMS Based-Plasma Metabolomics Reveals 3-O-Methyldopa as a New Biomarker of Poor Prognosis in High-Risk Neuroblastoma |
| title_sort | untargeted lc hrms based plasma metabolomics reveals 3 o methyldopa as a new biomarker of poor prognosis in high risk neuroblastoma |
| topic | neuroblastoma metabolomics biomarker high resolution mass spectrometry catecholamines 3-O-methyldopa |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.845936/full |
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