Human Plasma Metabolomics for Biomarker Discovery: Targeting the Molecular Subtypes in Breast Cancer

Purpose: The aim of this study is to identify differential metabolomic signatures in plasma samples of distinct subtypes of breast cancer patients that could be used in clinical practice as diagnostic biomarkers for these molecular phenotypes and to provide a more individualized and accurate therape...

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Main Authors: Leticia Díaz-Beltrán, Carmen González-Olmedo, Natalia Luque-Caro, Caridad Díaz, Ariadna Martín-Blázquez, Mónica Fernández-Navarro, Ana Laura Ortega-Granados, Fernando Gálvez-Montosa, Francisca Vicente, José Pérez del Palacio, Pedro Sánchez-Rovira
Format: Article
Language:English
Published: MDPI AG 2021-01-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/13/1/147
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author Leticia Díaz-Beltrán
Carmen González-Olmedo
Natalia Luque-Caro
Caridad Díaz
Ariadna Martín-Blázquez
Mónica Fernández-Navarro
Ana Laura Ortega-Granados
Fernando Gálvez-Montosa
Francisca Vicente
José Pérez del Palacio
Pedro Sánchez-Rovira
author_facet Leticia Díaz-Beltrán
Carmen González-Olmedo
Natalia Luque-Caro
Caridad Díaz
Ariadna Martín-Blázquez
Mónica Fernández-Navarro
Ana Laura Ortega-Granados
Fernando Gálvez-Montosa
Francisca Vicente
José Pérez del Palacio
Pedro Sánchez-Rovira
author_sort Leticia Díaz-Beltrán
collection DOAJ
description Purpose: The aim of this study is to identify differential metabolomic signatures in plasma samples of distinct subtypes of breast cancer patients that could be used in clinical practice as diagnostic biomarkers for these molecular phenotypes and to provide a more individualized and accurate therapeutic procedure. Methods: Untargeted LC-HRMS metabolomics approach in positive and negative electrospray ionization mode was used to analyze plasma samples from LA, LB, HER2+ and TN breast cancer patients and healthy controls in order to determine specific metabolomic profiles through univariate and multivariate statistical data analysis. Results: We tentatively identified altered metabolites displaying concentration variations among the four breast cancer molecular subtypes. We found a biomarker panel of 5 candidates in LA, 7 in LB, 5 in HER2 and 3 in TN that were able to discriminate each breast cancer subtype with a false discovery range corrected <i>p</i>-value < 0.05 and a fold-change cutoff value > 1.3. The model clinical value was evaluated with the AUROC, providing diagnostic capacities above 0.85. Conclusion: Our study identifies metabolic profiling differences in molecular phenotypes of breast cancer. This may represent a key step towards therapy improvement in personalized medicine and prioritization of tailored therapeutic intervention strategies.
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spelling doaj.art-ede90584cb8a4f619de82ab399a574012023-11-21T08:21:08ZengMDPI AGCancers2072-66942021-01-0113114710.3390/cancers13010147Human Plasma Metabolomics for Biomarker Discovery: Targeting the Molecular Subtypes in Breast CancerLeticia Díaz-Beltrán0Carmen González-Olmedo1Natalia Luque-Caro2Caridad Díaz3Ariadna Martín-Blázquez4Mónica Fernández-Navarro5Ana Laura Ortega-Granados6Fernando Gálvez-Montosa7Francisca Vicente8José Pérez del Palacio9Pedro Sánchez-Rovira10Medical Oncology Unit, University Hospital of Jaén, 23007 Jaén, Andalucía, SpainMedical Oncology Unit, University Hospital of Jaén, 23007 Jaén, Andalucía, SpainMedical Oncology Unit, University Hospital of Jaén, 23007 Jaén, Andalucía, SpainFundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía, 18016 Granada, Andalucía, SpainFundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía, 18016 Granada, Andalucía, SpainMedical Oncology Unit, University Hospital of Jaén, 23007 Jaén, Andalucía, SpainMedical Oncology Unit, University Hospital of Jaén, 23007 Jaén, Andalucía, SpainMedical Oncology Unit, University Hospital of Jaén, 23007 Jaén, Andalucía, SpainFundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía, 18016 Granada, Andalucía, SpainFundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía, 18016 Granada, Andalucía, SpainMedical Oncology Unit, University Hospital of Jaén, 23007 Jaén, Andalucía, SpainPurpose: The aim of this study is to identify differential metabolomic signatures in plasma samples of distinct subtypes of breast cancer patients that could be used in clinical practice as diagnostic biomarkers for these molecular phenotypes and to provide a more individualized and accurate therapeutic procedure. Methods: Untargeted LC-HRMS metabolomics approach in positive and negative electrospray ionization mode was used to analyze plasma samples from LA, LB, HER2+ and TN breast cancer patients and healthy controls in order to determine specific metabolomic profiles through univariate and multivariate statistical data analysis. Results: We tentatively identified altered metabolites displaying concentration variations among the four breast cancer molecular subtypes. We found a biomarker panel of 5 candidates in LA, 7 in LB, 5 in HER2 and 3 in TN that were able to discriminate each breast cancer subtype with a false discovery range corrected <i>p</i>-value < 0.05 and a fold-change cutoff value > 1.3. The model clinical value was evaluated with the AUROC, providing diagnostic capacities above 0.85. Conclusion: Our study identifies metabolic profiling differences in molecular phenotypes of breast cancer. This may represent a key step towards therapy improvement in personalized medicine and prioritization of tailored therapeutic intervention strategies.https://www.mdpi.com/2072-6694/13/1/147human plasma metabolomicsbreast cancermolecular subtypesmetabolic profilingpersonalized medicine
spellingShingle Leticia Díaz-Beltrán
Carmen González-Olmedo
Natalia Luque-Caro
Caridad Díaz
Ariadna Martín-Blázquez
Mónica Fernández-Navarro
Ana Laura Ortega-Granados
Fernando Gálvez-Montosa
Francisca Vicente
José Pérez del Palacio
Pedro Sánchez-Rovira
Human Plasma Metabolomics for Biomarker Discovery: Targeting the Molecular Subtypes in Breast Cancer
Cancers
human plasma metabolomics
breast cancer
molecular subtypes
metabolic profiling
personalized medicine
title Human Plasma Metabolomics for Biomarker Discovery: Targeting the Molecular Subtypes in Breast Cancer
title_full Human Plasma Metabolomics for Biomarker Discovery: Targeting the Molecular Subtypes in Breast Cancer
title_fullStr Human Plasma Metabolomics for Biomarker Discovery: Targeting the Molecular Subtypes in Breast Cancer
title_full_unstemmed Human Plasma Metabolomics for Biomarker Discovery: Targeting the Molecular Subtypes in Breast Cancer
title_short Human Plasma Metabolomics for Biomarker Discovery: Targeting the Molecular Subtypes in Breast Cancer
title_sort human plasma metabolomics for biomarker discovery targeting the molecular subtypes in breast cancer
topic human plasma metabolomics
breast cancer
molecular subtypes
metabolic profiling
personalized medicine
url https://www.mdpi.com/2072-6694/13/1/147
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