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

Autor: Stretch C; Department of Oncology, University of Calgary, Calgary, Canada., Aubin JM; Department of Surgery, University of Calgary, Calgary, Canada., Mickiewicz B; Department of Biological Sciences, University of Calgary, Calgary, Canada., Leugner D; Department of Surgery, University of Calgary, Calgary, Canada., Al-Manasra T; Department of Biological Sciences, University of Calgary, Calgary, Canada., Tobola E; Department of Surgery, University of Calgary, Calgary, Canada., Salazar S; Department of Surgery, University of Calgary, Calgary, Canada., Sutherland FR; Department of Surgery, University of Calgary, Calgary, Canada., Ball CG; Department of Surgery, University of Calgary, Calgary, Canada., Dixon E; Department of Surgery, University of Calgary, Calgary, Canada., Vogel HJ; Department of Biological Sciences, University of Calgary, Calgary, Canada., Damaraju S; Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Canada.; Department of Oncology, University of Alberta, Edmonton, Canada., Baracos VE; Department of Oncology, University of Alberta, Edmonton, Canada., Bathe OF; Department of Oncology, University of Calgary, Calgary, Canada.; Department of Surgery, University of Calgary, Calgary, Canada.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2018 May 03; Vol. 13 (5), pp. e0196235. Date of Electronic Publication: 2018 May 03 (Print Publication: 2018).
DOI: 10.1371/journal.pone.0196235
Abstrakt: 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.
Databáze: MEDLINE
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