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Targeted metabolomics detects a putatively diagnostic signature in plasma and dried blood spots from head and neck paraganglioma patients

Head and neck paragangliomas (HNPGLs), rare chemoresistant tumors curable only with surgery, are strongly influenced by genetic predisposition, hence patients and relatives require lifetime follow-up with MRI and/or PET-CT because of de novo disease risk. This entails exposure to electromagnetic/ion...

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Autores principales: De Fabritiis, Simone, Valentinuzzi, Silvia, Piras, Gianluca, Cicalini, Ilaria, Pieragostino, Damiana, Pagotto, Sara, Perconti, Silvia, Zucchelli, Mirco, Schena, Alberto, Taschin, Elisa, Berteşteanu, Gloria Simona, Esposito, Diana Liberata, Stigliano, Antonio, De Laurenzi, Vincenzo, Schiavi, Francesca, Sanna, Mario, Del Boccio, Piero, Verginelli, Fabio, Mariani-Costantini, Renato
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9968333/
https://www.ncbi.nlm.nih.gov/pubmed/36841802
http://dx.doi.org/10.1038/s41389-023-00456-4
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author De Fabritiis, Simone
Valentinuzzi, Silvia
Piras, Gianluca
Cicalini, Ilaria
Pieragostino, Damiana
Pagotto, Sara
Perconti, Silvia
Zucchelli, Mirco
Schena, Alberto
Taschin, Elisa
Berteşteanu, Gloria Simona
Esposito, Diana Liberata
Stigliano, Antonio
De Laurenzi, Vincenzo
Schiavi, Francesca
Sanna, Mario
Del Boccio, Piero
Verginelli, Fabio
Mariani-Costantini, Renato
author_facet De Fabritiis, Simone
Valentinuzzi, Silvia
Piras, Gianluca
Cicalini, Ilaria
Pieragostino, Damiana
Pagotto, Sara
Perconti, Silvia
Zucchelli, Mirco
Schena, Alberto
Taschin, Elisa
Berteşteanu, Gloria Simona
Esposito, Diana Liberata
Stigliano, Antonio
De Laurenzi, Vincenzo
Schiavi, Francesca
Sanna, Mario
Del Boccio, Piero
Verginelli, Fabio
Mariani-Costantini, Renato
author_sort De Fabritiis, Simone
collection PubMed
description Head and neck paragangliomas (HNPGLs), rare chemoresistant tumors curable only with surgery, are strongly influenced by genetic predisposition, hence patients and relatives require lifetime follow-up with MRI and/or PET-CT because of de novo disease risk. This entails exposure to electromagnetic/ionizing radiation, costs, and organizational challenges, because patients and relatives are scattered far from reference centers. Simplified first-line screening strategies are needed. We employed flow injection analysis tandem mass spectrometry, as used in newborn metabolic screening, to compare the plasma metabolic profile of HNPGL patients (59 samples, 56 cases) and healthy controls (24 samples, 24 cases). Principal Component Analysis (PCA) and Partial Least Discriminant Analysis (PLS-DA) highlighted a distinctive HNPGL signature, likely reflecting the anaplerotic conversion of the TCA cycle to glutaminolysis and catabolism of branched amino acids, DNA damage and deoxyadenosine (dAdo) accumulation, impairment of fatty acid oxidation, switch towards the Warburg effect and proinflammatory lysophosphatidylcholines (LPCs) signaling. Statistical analysis of the metabolites that most impacted on PLS-DA was extended to 10 acoustic neuroma and 2 cholesteatoma patients, confirming significant differences relative to the HNPGL plasma metabolomic profile. The best confusion matrix from the ROC curve built on 2 metabolites, dAdo and C26:0-LPC, provided specificity of 94.29% and sensitivity of 89.29%, with positive and negative predictive values of 96.2% and 84.6%, respectively. Analysis of dAdo and C26:0-LPC levels in dried venous and capillary blood confirmed that dAdo, likely deriving from 2′-deoxy-ATP accumulated in HNPGL cells following endogenous genotoxic damage, efficiently discriminated HNPGL patients from healthy controls and acoustic neuroma/cholesteatoma patients on easily manageable dried blood spots.
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spelling pubmed-99683332023-02-27 Targeted metabolomics detects a putatively diagnostic signature in plasma and dried blood spots from head and neck paraganglioma patients De Fabritiis, Simone Valentinuzzi, Silvia Piras, Gianluca Cicalini, Ilaria Pieragostino, Damiana Pagotto, Sara Perconti, Silvia Zucchelli, Mirco Schena, Alberto Taschin, Elisa Berteşteanu, Gloria Simona Esposito, Diana Liberata Stigliano, Antonio De Laurenzi, Vincenzo Schiavi, Francesca Sanna, Mario Del Boccio, Piero Verginelli, Fabio Mariani-Costantini, Renato Oncogenesis Article Head and neck paragangliomas (HNPGLs), rare chemoresistant tumors curable only with surgery, are strongly influenced by genetic predisposition, hence patients and relatives require lifetime follow-up with MRI and/or PET-CT because of de novo disease risk. This entails exposure to electromagnetic/ionizing radiation, costs, and organizational challenges, because patients and relatives are scattered far from reference centers. Simplified first-line screening strategies are needed. We employed flow injection analysis tandem mass spectrometry, as used in newborn metabolic screening, to compare the plasma metabolic profile of HNPGL patients (59 samples, 56 cases) and healthy controls (24 samples, 24 cases). Principal Component Analysis (PCA) and Partial Least Discriminant Analysis (PLS-DA) highlighted a distinctive HNPGL signature, likely reflecting the anaplerotic conversion of the TCA cycle to glutaminolysis and catabolism of branched amino acids, DNA damage and deoxyadenosine (dAdo) accumulation, impairment of fatty acid oxidation, switch towards the Warburg effect and proinflammatory lysophosphatidylcholines (LPCs) signaling. Statistical analysis of the metabolites that most impacted on PLS-DA was extended to 10 acoustic neuroma and 2 cholesteatoma patients, confirming significant differences relative to the HNPGL plasma metabolomic profile. The best confusion matrix from the ROC curve built on 2 metabolites, dAdo and C26:0-LPC, provided specificity of 94.29% and sensitivity of 89.29%, with positive and negative predictive values of 96.2% and 84.6%, respectively. Analysis of dAdo and C26:0-LPC levels in dried venous and capillary blood confirmed that dAdo, likely deriving from 2′-deoxy-ATP accumulated in HNPGL cells following endogenous genotoxic damage, efficiently discriminated HNPGL patients from healthy controls and acoustic neuroma/cholesteatoma patients on easily manageable dried blood spots. Nature Publishing Group UK 2023-02-25 /pmc/articles/PMC9968333/ /pubmed/36841802 http://dx.doi.org/10.1038/s41389-023-00456-4 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
De Fabritiis, Simone
Valentinuzzi, Silvia
Piras, Gianluca
Cicalini, Ilaria
Pieragostino, Damiana
Pagotto, Sara
Perconti, Silvia
Zucchelli, Mirco
Schena, Alberto
Taschin, Elisa
Berteşteanu, Gloria Simona
Esposito, Diana Liberata
Stigliano, Antonio
De Laurenzi, Vincenzo
Schiavi, Francesca
Sanna, Mario
Del Boccio, Piero
Verginelli, Fabio
Mariani-Costantini, Renato
Targeted metabolomics detects a putatively diagnostic signature in plasma and dried blood spots from head and neck paraganglioma patients
title Targeted metabolomics detects a putatively diagnostic signature in plasma and dried blood spots from head and neck paraganglioma patients
title_full Targeted metabolomics detects a putatively diagnostic signature in plasma and dried blood spots from head and neck paraganglioma patients
title_fullStr Targeted metabolomics detects a putatively diagnostic signature in plasma and dried blood spots from head and neck paraganglioma patients
title_full_unstemmed Targeted metabolomics detects a putatively diagnostic signature in plasma and dried blood spots from head and neck paraganglioma patients
title_short Targeted metabolomics detects a putatively diagnostic signature in plasma and dried blood spots from head and neck paraganglioma patients
title_sort targeted metabolomics detects a putatively diagnostic signature in plasma and dried blood spots from head and neck paraganglioma patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9968333/
https://www.ncbi.nlm.nih.gov/pubmed/36841802
http://dx.doi.org/10.1038/s41389-023-00456-4
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