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Metabolomic Analysis of Plasma from Breast Cancer Patients Using Ultra-High-Performance Liquid Chromatography Coupled with Mass Spectrometry: An Untargeted Study
Breast cancer (BC) is one of the leading causes of cancer mortality in women worldwide, and therefore, novel biomarkers for early disease detection are critically needed. We performed herein an untargeted plasma metabolomic profiling of 55 BC patients and 55 healthy controls (HC) using ultra-high pe...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9147455/ https://www.ncbi.nlm.nih.gov/pubmed/35629952 http://dx.doi.org/10.3390/metabo12050447 |
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author | Da Cunha, Patricia A. Nitusca, Diana Canto, Luisa Matos Do Varghese, Rency S. Ressom, Habtom W. Willey, Shawna Marian, Catalin Haddad, Bassem R. |
author_facet | Da Cunha, Patricia A. Nitusca, Diana Canto, Luisa Matos Do Varghese, Rency S. Ressom, Habtom W. Willey, Shawna Marian, Catalin Haddad, Bassem R. |
author_sort | Da Cunha, Patricia A. |
collection | PubMed |
description | Breast cancer (BC) is one of the leading causes of cancer mortality in women worldwide, and therefore, novel biomarkers for early disease detection are critically needed. We performed herein an untargeted plasma metabolomic profiling of 55 BC patients and 55 healthy controls (HC) using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF-MS). Pre-processed data revealed 2494 ions in total. Data matrices’ paired t-tests revealed 792 ions (both positive and negative) which presented statistically significant changes (FDR < 0.05) in intensity levels between cases versus controls. Metabolites identified with putative names via MetaboQuest using MS/MS and mass-based approaches included amino acid esters (i.e., N-stearoyl tryptophan, L-arginine ethyl ester), dipeptides (ile-ser, met-his), nitrogenous bases (i.e., uracil derivatives), lipid metabolism-derived molecules (caproleic acid), and exogenous compounds from plants, drugs, or dietary supplements. LASSO regression selected 16 metabolites after several variables (TNM Stage, Grade, smoking status, menopausal status, and race) were adjusted. A predictive conditional logistic regression model on the 16 LASSO selected ions provided a high diagnostic performance with an area-under-the-curve (AUC) value of 0.9729 (95% CI 0.96–0.98) on all 55 samples. This study proves that BC possesses a specific metabolic signature that could be exploited as a novel metabolomics-based approach for BC detection and characterization. Future studies of large-scale cohorts are needed to validate these findings. |
format | Online Article Text |
id | pubmed-9147455 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91474552022-05-29 Metabolomic Analysis of Plasma from Breast Cancer Patients Using Ultra-High-Performance Liquid Chromatography Coupled with Mass Spectrometry: An Untargeted Study Da Cunha, Patricia A. Nitusca, Diana Canto, Luisa Matos Do Varghese, Rency S. Ressom, Habtom W. Willey, Shawna Marian, Catalin Haddad, Bassem R. Metabolites Article Breast cancer (BC) is one of the leading causes of cancer mortality in women worldwide, and therefore, novel biomarkers for early disease detection are critically needed. We performed herein an untargeted plasma metabolomic profiling of 55 BC patients and 55 healthy controls (HC) using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF-MS). Pre-processed data revealed 2494 ions in total. Data matrices’ paired t-tests revealed 792 ions (both positive and negative) which presented statistically significant changes (FDR < 0.05) in intensity levels between cases versus controls. Metabolites identified with putative names via MetaboQuest using MS/MS and mass-based approaches included amino acid esters (i.e., N-stearoyl tryptophan, L-arginine ethyl ester), dipeptides (ile-ser, met-his), nitrogenous bases (i.e., uracil derivatives), lipid metabolism-derived molecules (caproleic acid), and exogenous compounds from plants, drugs, or dietary supplements. LASSO regression selected 16 metabolites after several variables (TNM Stage, Grade, smoking status, menopausal status, and race) were adjusted. A predictive conditional logistic regression model on the 16 LASSO selected ions provided a high diagnostic performance with an area-under-the-curve (AUC) value of 0.9729 (95% CI 0.96–0.98) on all 55 samples. This study proves that BC possesses a specific metabolic signature that could be exploited as a novel metabolomics-based approach for BC detection and characterization. Future studies of large-scale cohorts are needed to validate these findings. MDPI 2022-05-17 /pmc/articles/PMC9147455/ /pubmed/35629952 http://dx.doi.org/10.3390/metabo12050447 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Da Cunha, Patricia A. Nitusca, Diana Canto, Luisa Matos Do Varghese, Rency S. Ressom, Habtom W. Willey, Shawna Marian, Catalin Haddad, Bassem R. Metabolomic Analysis of Plasma from Breast Cancer Patients Using Ultra-High-Performance Liquid Chromatography Coupled with Mass Spectrometry: An Untargeted Study |
title | Metabolomic Analysis of Plasma from Breast Cancer Patients Using Ultra-High-Performance Liquid Chromatography Coupled with Mass Spectrometry: An Untargeted Study |
title_full | Metabolomic Analysis of Plasma from Breast Cancer Patients Using Ultra-High-Performance Liquid Chromatography Coupled with Mass Spectrometry: An Untargeted Study |
title_fullStr | Metabolomic Analysis of Plasma from Breast Cancer Patients Using Ultra-High-Performance Liquid Chromatography Coupled with Mass Spectrometry: An Untargeted Study |
title_full_unstemmed | Metabolomic Analysis of Plasma from Breast Cancer Patients Using Ultra-High-Performance Liquid Chromatography Coupled with Mass Spectrometry: An Untargeted Study |
title_short | Metabolomic Analysis of Plasma from Breast Cancer Patients Using Ultra-High-Performance Liquid Chromatography Coupled with Mass Spectrometry: An Untargeted Study |
title_sort | metabolomic analysis of plasma from breast cancer patients using ultra-high-performance liquid chromatography coupled with mass spectrometry: an untargeted study |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9147455/ https://www.ncbi.nlm.nih.gov/pubmed/35629952 http://dx.doi.org/10.3390/metabo12050447 |
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