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Metabolic Biomarkers for the Early Detection of Cancer Cachexia

Background: Cancer cachexia is a severe metabolic disorder characterized by progressive weight loss along with a dramatic loss in skeletal muscle and adipose tissue. Like cancer, cachexia progresses in stages starting with pre-cachexia to cachexia and finally to refractory cachexia. In the refractor...

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Autores principales: O’Connell, Thomas M., Golzarri-Arroyo, Lilian, Pin, Fabrizio, Barreto, Rafael, Dickinson, Stephanie L., Couch, Marion E., Bonetto, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490779/
https://www.ncbi.nlm.nih.gov/pubmed/34621740
http://dx.doi.org/10.3389/fcell.2021.720096
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author O’Connell, Thomas M.
Golzarri-Arroyo, Lilian
Pin, Fabrizio
Barreto, Rafael
Dickinson, Stephanie L.
Couch, Marion E.
Bonetto, Andrea
author_facet O’Connell, Thomas M.
Golzarri-Arroyo, Lilian
Pin, Fabrizio
Barreto, Rafael
Dickinson, Stephanie L.
Couch, Marion E.
Bonetto, Andrea
author_sort O’Connell, Thomas M.
collection PubMed
description Background: Cancer cachexia is a severe metabolic disorder characterized by progressive weight loss along with a dramatic loss in skeletal muscle and adipose tissue. Like cancer, cachexia progresses in stages starting with pre-cachexia to cachexia and finally to refractory cachexia. In the refractory stage, patients are no longer responsive to therapy and management of weight loss is no longer possible. It is therefore critical to detect cachexia as early as possible. In this study we applied a metabolomics approach to search for early biomarkers of cachexia. Methods: Multi-platform metabolomics analyses were applied to the murine Colon-26 (C26) model of cachexia. Tumor bearing mice (n = 5) were sacrificed every other day over the 14-day time course and control mice (n = 5) were sacrificed every fourth day starting at day 2. Linear regression modeling of the data yielded metabolic trajectories that were compared with the trajectories of body weight and skeletal muscle loss to look for early biomarkers of cachexia. Results: Weight loss in the tumor-bearing mice became significant at day 9 as did the loss of tibialis muscle. The loss of muscle in the gastrocnemius and quadriceps was significant at day 7. Reductions in amino acids were among the earliest metabolic biomarkers of cachexia. The earliest change was in methionine at day 4. Significant alterations in acylcarnitines and lipoproteins were also detected several days prior to weight loss. Conclusion: The results of this study demonstrate that metabolic alterations appear well in advance of observable weight loss. The earliest and most significant alterations were found in amino acids and lipoproteins. Validation of these results in other models of cachexia and in clinical studies will pave the way for a clinical diagnostic panel for the early detection of cachexia. Such a panel would provide a tremendous advance in cachectic patient management and in the design of clinical trials for new therapeutic interventions.
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spelling pubmed-84907792021-10-06 Metabolic Biomarkers for the Early Detection of Cancer Cachexia O’Connell, Thomas M. Golzarri-Arroyo, Lilian Pin, Fabrizio Barreto, Rafael Dickinson, Stephanie L. Couch, Marion E. Bonetto, Andrea Front Cell Dev Biol Cell and Developmental Biology Background: Cancer cachexia is a severe metabolic disorder characterized by progressive weight loss along with a dramatic loss in skeletal muscle and adipose tissue. Like cancer, cachexia progresses in stages starting with pre-cachexia to cachexia and finally to refractory cachexia. In the refractory stage, patients are no longer responsive to therapy and management of weight loss is no longer possible. It is therefore critical to detect cachexia as early as possible. In this study we applied a metabolomics approach to search for early biomarkers of cachexia. Methods: Multi-platform metabolomics analyses were applied to the murine Colon-26 (C26) model of cachexia. Tumor bearing mice (n = 5) were sacrificed every other day over the 14-day time course and control mice (n = 5) were sacrificed every fourth day starting at day 2. Linear regression modeling of the data yielded metabolic trajectories that were compared with the trajectories of body weight and skeletal muscle loss to look for early biomarkers of cachexia. Results: Weight loss in the tumor-bearing mice became significant at day 9 as did the loss of tibialis muscle. The loss of muscle in the gastrocnemius and quadriceps was significant at day 7. Reductions in amino acids were among the earliest metabolic biomarkers of cachexia. The earliest change was in methionine at day 4. Significant alterations in acylcarnitines and lipoproteins were also detected several days prior to weight loss. Conclusion: The results of this study demonstrate that metabolic alterations appear well in advance of observable weight loss. The earliest and most significant alterations were found in amino acids and lipoproteins. Validation of these results in other models of cachexia and in clinical studies will pave the way for a clinical diagnostic panel for the early detection of cachexia. Such a panel would provide a tremendous advance in cachectic patient management and in the design of clinical trials for new therapeutic interventions. Frontiers Media S.A. 2021-09-21 /pmc/articles/PMC8490779/ /pubmed/34621740 http://dx.doi.org/10.3389/fcell.2021.720096 Text en Copyright © 2021 O’Connell, Golzarri-Arroyo, Pin, Barreto, Dickinson, Couch and Bonetto. https://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 Cell and Developmental Biology
O’Connell, Thomas M.
Golzarri-Arroyo, Lilian
Pin, Fabrizio
Barreto, Rafael
Dickinson, Stephanie L.
Couch, Marion E.
Bonetto, Andrea
Metabolic Biomarkers for the Early Detection of Cancer Cachexia
title Metabolic Biomarkers for the Early Detection of Cancer Cachexia
title_full Metabolic Biomarkers for the Early Detection of Cancer Cachexia
title_fullStr Metabolic Biomarkers for the Early Detection of Cancer Cachexia
title_full_unstemmed Metabolic Biomarkers for the Early Detection of Cancer Cachexia
title_short Metabolic Biomarkers for the Early Detection of Cancer Cachexia
title_sort metabolic biomarkers for the early detection of cancer cachexia
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490779/
https://www.ncbi.nlm.nih.gov/pubmed/34621740
http://dx.doi.org/10.3389/fcell.2021.720096
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