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Clinical Metabolomics Identifies Blood Serum Branched Chain Amino Acids as Potential Predictive Biomarkers for Chronic Graft vs. Host Disease

The allogeneic hematopoietic stem cell transplantation procedure—the only curative therapy for many types of hematological cancers—is increasing, and graft vs. host disease (GVHD) is the main cause of morbidity and mortality after transplantation. Currently, GVHD diagnosis is clinically performed. W...

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Autores principales: Alborghetti, Marcos Rodrigo, Correa, Maria Elvira Pizzigatti, Whangbo, Jennifer, Shi, Xu, Aricetti, Juliana Aparecida, da Silva, Andreia Aparecida, Miranda, Eliana Cristina Martins, Sforca, Mauricio Luis, Caldana, Camila, Gerszten, Robert E., Ritz, Jerome, Zeri, Ana Carolina de Mattos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436081/
https://www.ncbi.nlm.nih.gov/pubmed/30949447
http://dx.doi.org/10.3389/fonc.2019.00141
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author Alborghetti, Marcos Rodrigo
Correa, Maria Elvira Pizzigatti
Whangbo, Jennifer
Shi, Xu
Aricetti, Juliana Aparecida
da Silva, Andreia Aparecida
Miranda, Eliana Cristina Martins
Sforca, Mauricio Luis
Caldana, Camila
Gerszten, Robert E.
Ritz, Jerome
Zeri, Ana Carolina de Mattos
author_facet Alborghetti, Marcos Rodrigo
Correa, Maria Elvira Pizzigatti
Whangbo, Jennifer
Shi, Xu
Aricetti, Juliana Aparecida
da Silva, Andreia Aparecida
Miranda, Eliana Cristina Martins
Sforca, Mauricio Luis
Caldana, Camila
Gerszten, Robert E.
Ritz, Jerome
Zeri, Ana Carolina de Mattos
author_sort Alborghetti, Marcos Rodrigo
collection PubMed
description The allogeneic hematopoietic stem cell transplantation procedure—the only curative therapy for many types of hematological cancers—is increasing, and graft vs. host disease (GVHD) is the main cause of morbidity and mortality after transplantation. Currently, GVHD diagnosis is clinically performed. Whereas, biomarker panels have been developed for acute GVHD (aGVHD), there is a lack of information about the chronic form (cGVHD). Using nuclear magnetic resonance (NMR) and gas chromatography coupled to time-of-flight (GC-TOF) mass spectrometry, this study prospectively evaluated the serum metabolome of 18 Brazilian patients who had undergone allogeneic hematopoietic stem cell transplantation (HSCT). We identified and quantified 63 metabolites and performed the metabolomic profile on day −10, day 0, day +10 and day +100, in reference to day of transplantation. Patients did not present aGVHD or cGVHD clinical symptoms at sampling times. From 18 patients analyzed, 6 developed cGVHD. The branched-chain amino acids (BCAAs) leucine and isoleucine were reduced and the sulfur-containing metabolite (cystine) was increased at day +10 and day +100. The area under receiver operating characteristics (ROC) curves was higher than 0.79. BCAA findings were validated by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) in 49 North American patients at day +100; however, cystine findings were not statistically significant in this patient set. Our results highlight the importance of multi-temporal and multivariate biomarker panels for predicting and understanding cGVHD.
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spelling pubmed-64360812019-04-04 Clinical Metabolomics Identifies Blood Serum Branched Chain Amino Acids as Potential Predictive Biomarkers for Chronic Graft vs. Host Disease Alborghetti, Marcos Rodrigo Correa, Maria Elvira Pizzigatti Whangbo, Jennifer Shi, Xu Aricetti, Juliana Aparecida da Silva, Andreia Aparecida Miranda, Eliana Cristina Martins Sforca, Mauricio Luis Caldana, Camila Gerszten, Robert E. Ritz, Jerome Zeri, Ana Carolina de Mattos Front Oncol Oncology The allogeneic hematopoietic stem cell transplantation procedure—the only curative therapy for many types of hematological cancers—is increasing, and graft vs. host disease (GVHD) is the main cause of morbidity and mortality after transplantation. Currently, GVHD diagnosis is clinically performed. Whereas, biomarker panels have been developed for acute GVHD (aGVHD), there is a lack of information about the chronic form (cGVHD). Using nuclear magnetic resonance (NMR) and gas chromatography coupled to time-of-flight (GC-TOF) mass spectrometry, this study prospectively evaluated the serum metabolome of 18 Brazilian patients who had undergone allogeneic hematopoietic stem cell transplantation (HSCT). We identified and quantified 63 metabolites and performed the metabolomic profile on day −10, day 0, day +10 and day +100, in reference to day of transplantation. Patients did not present aGVHD or cGVHD clinical symptoms at sampling times. From 18 patients analyzed, 6 developed cGVHD. The branched-chain amino acids (BCAAs) leucine and isoleucine were reduced and the sulfur-containing metabolite (cystine) was increased at day +10 and day +100. The area under receiver operating characteristics (ROC) curves was higher than 0.79. BCAA findings were validated by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) in 49 North American patients at day +100; however, cystine findings were not statistically significant in this patient set. Our results highlight the importance of multi-temporal and multivariate biomarker panels for predicting and understanding cGVHD. Frontiers Media S.A. 2019-03-18 /pmc/articles/PMC6436081/ /pubmed/30949447 http://dx.doi.org/10.3389/fonc.2019.00141 Text en Copyright © 2019 Alborghetti, Correa, Whangbo, Shi, Aricetti, Silva, Miranda, Sforca, Caldana, Gerszten, Ritz and Zeri. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Alborghetti, Marcos Rodrigo
Correa, Maria Elvira Pizzigatti
Whangbo, Jennifer
Shi, Xu
Aricetti, Juliana Aparecida
da Silva, Andreia Aparecida
Miranda, Eliana Cristina Martins
Sforca, Mauricio Luis
Caldana, Camila
Gerszten, Robert E.
Ritz, Jerome
Zeri, Ana Carolina de Mattos
Clinical Metabolomics Identifies Blood Serum Branched Chain Amino Acids as Potential Predictive Biomarkers for Chronic Graft vs. Host Disease
title Clinical Metabolomics Identifies Blood Serum Branched Chain Amino Acids as Potential Predictive Biomarkers for Chronic Graft vs. Host Disease
title_full Clinical Metabolomics Identifies Blood Serum Branched Chain Amino Acids as Potential Predictive Biomarkers for Chronic Graft vs. Host Disease
title_fullStr Clinical Metabolomics Identifies Blood Serum Branched Chain Amino Acids as Potential Predictive Biomarkers for Chronic Graft vs. Host Disease
title_full_unstemmed Clinical Metabolomics Identifies Blood Serum Branched Chain Amino Acids as Potential Predictive Biomarkers for Chronic Graft vs. Host Disease
title_short Clinical Metabolomics Identifies Blood Serum Branched Chain Amino Acids as Potential Predictive Biomarkers for Chronic Graft vs. Host Disease
title_sort clinical metabolomics identifies blood serum branched chain amino acids as potential predictive biomarkers for chronic graft vs. host disease
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436081/
https://www.ncbi.nlm.nih.gov/pubmed/30949447
http://dx.doi.org/10.3389/fonc.2019.00141
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