Cited by 144Nutrition and Health in AgingPancreatic and Hepatic Oncology ResearchMuscle Physiology and Disorders

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

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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.·2018·PLOS ONE

DOI 10.1371/journal.pone.0196235PMC PMC5933771

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Abstract

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) 1H-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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Fig 1 Body composition in patients with periampullary adenocarcinomas. A. Representative axial CT images from a muscular patient with high radiodensity (left panel), a patient with sarcopenia but high radiodensity (middle panel) and a patient with low muscularity and low radiodensity (right panel). The horizontal bar shows the Hounsfield Unit ranges pertaining to the isolated CT rectangles showing only the paraspinal muscles. B. Dot plot illustrating the association of muscle mass and radiodensity, in males and females. C. Differences in adipose tissue distribution in individuals with sarcopenia and low muscle radiodensity.CC BY · PubMed Central

Fig 2 Kaplan-Meier plots. (A) Disease-free survival (DFS) as a function of sarcopenia. (B) Overall survival (OS) as a function of sarcopenia. (C) DFS as a function of myosteatosis. (D) OS as a function of myosteatosis. (E) DFS in individuals with both sarcopenia and myosteatosis. (F) OS in individuals with both sarcopenia and myosteatosis.CC BY · PubMed Central

Fig 3 Summary of transcriptomic analysis. (A) Heatmap showing top 100 most differentially abundant transcripts (based on p-value), sarcopenia vs. normal body composition. (B) A heatmap showing top 100 most differentially abundant transcripts (based on p-value), myosteatosis vs. normal body composition. (C) Venn diagram summarizing numbers of unique and shared differentially abundant genes in sarcopenia and myosteatosis.CC BY · PubMed Central

Fig 4 Biological functions associated with differentially abundant genes for muscle radiodensity and sarcopenia.CC BY · PubMed Central

Fig 5 Metabolomic models that distinguish body composition phenotypes in pancreatic cancer patients. (A) OPLS-DA scores plots and metabolite lists for NMR and GC-MS metabolites: sarcopenia vs. no sarcopenia or myosteatosis. (B) OPLS-DA scores plots and metabolite lists for NMR and GC-MS metabolites: myosteatosis vs. no sarcopenia or myosteatosis. For the metabolite lists: metabolites in bold are shared in 1H-NMR spectroscopy and GC-MS datasets; metabolites in red have a VIP>1.CC BY · PubMed Central

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Authors: Stretch, C., Aubin, J.-M., Mickiewicz, B., Leugner, D., Al-manasra, T., Tobola, E., Salazar, S., Sutherland, F. R., Ball, C. G., Dixon, E., Vogel, H. J., Damaraju, S., Baracos, V. E., & Bathe, O. F.
Affiliations: University of Calgary (CA)
University of Alberta (CA)
Corresponding author: Bathe, Oliver F.
ORCID: Stretch, Cynthia
Mickiewicz, Beata
Salazar, Santiago
Ball, Chad G.
Dixon, Elijah
Vogel, Hans J.
Baracos, Vickie E.
Bathe, Oliver F.
Venue: PLOS ONE
Publisher: Public Library of Science (PLoS)
Published: 2018-05-03
Volume: 13
Issue: 5
Pages: e0196235
ISSN: 1932-6203 (ISSN-L)
DOI: 10.1371/journal.pone.0196235
PMC: PMC5933771
OpenAlex: W2799934298
Cited by: 144
References: 41
Citations by year: 2026: 13 · 2025: 12 · 2024: 19 · 2023: 20 · 2022: 14 · 2021: 24 · 2020: 23 · 2019: 16 · 2018: 3
FWCI: 11.31
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: PLoS ONE (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Figshare (submittedVersion, cc-by)
Funders: Alberta Innovates
Canadian Institutes of Health Research
Alberta Cancer Foundation
Topics: Health Sciences › Medicine › Physiology (medical) › Nutrition and Health in Aging
Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
Keywords: sarcopenia, myosteatosis, pancreatic ductal adenocarcinoma, periampullary adenocarcinoma, body composition, rectus abdominis, serum metabolome, subcutaneous adipose tissue, visceral adipose tissue, body fat distribution, survival, oxidative phosphorylation, lipid accumulation, inflammation, carbohydrate metabolism, pancreaticoduodenectomy
MeSH terms: Adenocarcinoma, Adipose Tissue, Aged, Body Composition, Duodenal Neoplasms, Female, Humans, Male, Middle Aged, Muscles, Pancreatic Neoplasms, Ampulla of Vater, Gene Expression Profiling, Metabolomics, Sarcopenia

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

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