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Sarcopenia and myosteatosis are accompanied by distinct biological profiles in patients with pancreatic and periampullary adenocarcinomas

INTRODUCTION: Pancreatic and periampullary adenocarcinomas are associated with abnormal body composition visible on CT scans, including low muscle mass (sarcopenia) and low muscle radiodensity due to fat infiltration in muscle (myosteatosis). The biological and clinical correlates to these features...

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Autores principales: Stretch, Cynthia, Aubin, Jean-Michel, Mickiewicz, Beata, Leugner, Derek, Al-manasra, Tariq, Tobola, Elizabeth, Salazar, Santiago, Sutherland, Francis R., Ball, Chad G., Dixon, Elijah, Vogel, Hans J., Damaraju, Sambasivario, Baracos, Vickie E., Bathe, Oliver F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5933771/
https://www.ncbi.nlm.nih.gov/pubmed/29723245
http://dx.doi.org/10.1371/journal.pone.0196235
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author Stretch, Cynthia
Aubin, Jean-Michel
Mickiewicz, Beata
Leugner, Derek
Al-manasra, Tariq
Tobola, Elizabeth
Salazar, Santiago
Sutherland, Francis R.
Ball, Chad G.
Dixon, Elijah
Vogel, Hans J.
Damaraju, Sambasivario
Baracos, Vickie E.
Bathe, Oliver F.
author_facet Stretch, Cynthia
Aubin, Jean-Michel
Mickiewicz, Beata
Leugner, Derek
Al-manasra, Tariq
Tobola, Elizabeth
Salazar, Santiago
Sutherland, Francis R.
Ball, Chad G.
Dixon, Elijah
Vogel, Hans J.
Damaraju, Sambasivario
Baracos, Vickie E.
Bathe, Oliver F.
author_sort Stretch, Cynthia
collection PubMed
description INTRODUCTION: Pancreatic and periampullary adenocarcinomas are associated with abnormal body composition visible on CT scans, including low muscle mass (sarcopenia) and low muscle radiodensity due to fat infiltration in muscle (myosteatosis). The biological and clinical correlates to these features are poorly understood. METHODS: Clinical characteristics and outcomes were studied in 123 patients who underwent pancreaticoduodenectomy for pancreatic or non-pancreatic periampullary adenocarcinoma and who had available preoperative CT scans. In a subgroup of patients with pancreatic cancer (n = 29), rectus abdominus muscle mRNA expression was determined by cDNA microarray and in another subgroup (n = 29) (1)H-NMR spectroscopy and gas chromatography-mass spectrometry were used to characterize the serum metabolome. RESULTS: Muscle mass and radiodensity were not significantly correlated. Distinct groups were identified: sarcopenia (40.7%), myosteatosis (25.2%), both (11.4%). Fat distribution differed in these groups; sarcopenia associated with lower subcutaneous adipose tissue (P<0.0001) and myosteatosis associated with greater visceral adipose tissue (P<0.0001). Sarcopenia, myosteatosis and their combined presence associated with shorter survival, Log Rank P = 0.005, P = 0.06, and P = 0.002, respectively. In muscle, transcriptomic analysis suggested increased inflammation and decreased growth in sarcopenia and disrupted oxidative phosphorylation and lipid accumulation in myosteatosis. In the circulating metabolome, metabolites consistent with muscle catabolism associated with sarcopenia. Metabolites consistent with disordered carbohydrate metabolism were identified in both sarcopenia and myosteatosis. DISCUSSION: Muscle phenotypes differ clinically and biologically. Because these muscle phenotypes are linked to poor survival, it will be imperative to delineate their pathophysiologic mechanisms, including whether they are driven by variable tumor biology or host response.
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spelling pubmed-59337712018-05-18 Sarcopenia and myosteatosis are accompanied by distinct biological profiles in patients with pancreatic and periampullary adenocarcinomas Stretch, Cynthia Aubin, Jean-Michel Mickiewicz, Beata Leugner, Derek Al-manasra, Tariq Tobola, Elizabeth Salazar, Santiago Sutherland, Francis R. Ball, Chad G. Dixon, Elijah Vogel, Hans J. Damaraju, Sambasivario Baracos, Vickie E. Bathe, Oliver F. PLoS One Research Article INTRODUCTION: Pancreatic and periampullary adenocarcinomas are associated with abnormal body composition visible on CT scans, including low muscle mass (sarcopenia) and low muscle radiodensity due to fat infiltration in muscle (myosteatosis). The biological and clinical correlates to these features are poorly understood. METHODS: Clinical characteristics and outcomes were studied in 123 patients who underwent pancreaticoduodenectomy for pancreatic or non-pancreatic periampullary adenocarcinoma and who had available preoperative CT scans. In a subgroup of patients with pancreatic cancer (n = 29), rectus abdominus muscle mRNA expression was determined by cDNA microarray and in another subgroup (n = 29) (1)H-NMR spectroscopy and gas chromatography-mass spectrometry were used to characterize the serum metabolome. RESULTS: Muscle mass and radiodensity were not significantly correlated. Distinct groups were identified: sarcopenia (40.7%), myosteatosis (25.2%), both (11.4%). Fat distribution differed in these groups; sarcopenia associated with lower subcutaneous adipose tissue (P<0.0001) and myosteatosis associated with greater visceral adipose tissue (P<0.0001). Sarcopenia, myosteatosis and their combined presence associated with shorter survival, Log Rank P = 0.005, P = 0.06, and P = 0.002, respectively. In muscle, transcriptomic analysis suggested increased inflammation and decreased growth in sarcopenia and disrupted oxidative phosphorylation and lipid accumulation in myosteatosis. In the circulating metabolome, metabolites consistent with muscle catabolism associated with sarcopenia. Metabolites consistent with disordered carbohydrate metabolism were identified in both sarcopenia and myosteatosis. DISCUSSION: Muscle phenotypes differ clinically and biologically. Because these muscle phenotypes are linked to poor survival, it will be imperative to delineate their pathophysiologic mechanisms, including whether they are driven by variable tumor biology or host response. Public Library of Science 2018-05-03 /pmc/articles/PMC5933771/ /pubmed/29723245 http://dx.doi.org/10.1371/journal.pone.0196235 Text en © 2018 Stretch et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Stretch, Cynthia
Aubin, Jean-Michel
Mickiewicz, Beata
Leugner, Derek
Al-manasra, Tariq
Tobola, Elizabeth
Salazar, Santiago
Sutherland, Francis R.
Ball, Chad G.
Dixon, Elijah
Vogel, Hans J.
Damaraju, Sambasivario
Baracos, Vickie E.
Bathe, Oliver F.
Sarcopenia and myosteatosis are accompanied by distinct biological profiles in patients with pancreatic and periampullary adenocarcinomas
title Sarcopenia and myosteatosis are accompanied by distinct biological profiles in patients with pancreatic and periampullary adenocarcinomas
title_full Sarcopenia and myosteatosis are accompanied by distinct biological profiles in patients with pancreatic and periampullary adenocarcinomas
title_fullStr Sarcopenia and myosteatosis are accompanied by distinct biological profiles in patients with pancreatic and periampullary adenocarcinomas
title_full_unstemmed Sarcopenia and myosteatosis are accompanied by distinct biological profiles in patients with pancreatic and periampullary adenocarcinomas
title_short Sarcopenia and myosteatosis are accompanied by distinct biological profiles in patients with pancreatic and periampullary adenocarcinomas
title_sort sarcopenia and myosteatosis are accompanied by distinct biological profiles in patients with pancreatic and periampullary adenocarcinomas
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5933771/
https://www.ncbi.nlm.nih.gov/pubmed/29723245
http://dx.doi.org/10.1371/journal.pone.0196235
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