title: Metabolomics evaluation of serum markers for cachexia and their intra-day variation in patients with advanced pancreatic cancer.
abstract: OBJECTIVE
  Cancer cachexia is a multifactorial syndrome characterized by progressive loss of weight and muscle atrophy. Using metabolomics, we investigated serum markers and their intra-day variation in advanced pancreatic cancer patients with cachexia.
  
  
  METHODS
  Patients were enrolled in two groups: those with or without cachexia. Blood samples collected at 6:30 AM, 11:30 AM, 4:30 PM, and 9:30 PM were analyzed using metabolomics, and serum levels of IL-6, TNF-α, and leptin were measured and compared between the two groups. Intra-day variation was then evaluated.
  
  
  RESULTS
  Twenty-one patients were enrolled in total. In the cachexia group (n = 9), median body weight loss rate over 6 months was greater, performance status was poorer, and anorexia was more severe than in the non-cachexia group (n = 12). Each metabolites level showed substantial intra-day variation, and some of them displayed significant differences between the two groups. Levels of paraxanthine remained markedly lower in the cohort with cachexia at all measurement points. Besides, median IL-6 and TNF-α levels appeared higher and leptin concentration appeared lower in the cachexia group, albeit without statistical significance.
  
  
  CONCLUSIONS
  Some metabolites and some serological marker levels were affected by cancer cachexia. Although paraxanthine levels were consistently lower in patients with cachexia, we identified that many metabolites indicated large intra- and inter-day variation and that it might be necessary to pay attention to intra-day variation in metabolomics research.
authors.affiliation: Division of Medical Oncology/Hematology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Fujiwara
authors.affiliation: Division of Gastroenterology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Division of Medical Oncology/Hematology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Chayahara
authors.affiliation: Division of Medical Oncology/Hematology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Imamura
authors.affiliation: Division of Medical Oncology/Hematology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Toyoda
authors.affiliation: Division of Medical Oncology/Hematology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Kiyota
authors.affiliation: Division of Medical Oncology/Hematology, Kobe University Graduate School of Medicine, Kobe, Japan; Cancer Center, Kobe University Hospital, Kobe, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Mukohara
authors.affiliation: Division of Gastroenterology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Nishiumi
authors.affiliation: Division of Gastroenterology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Azuma
authors.affiliation: Division of Gastroenterology, Kobe University Graduate School of Medicine, Kobe, Japan; Division of Metabolomics Research, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: Division of Medical Oncology/Hematology, Kobe University Graduate School of Medicine, Kobe, Japan; Cancer Center, Kobe University Hospital, Kobe, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Minami
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D002100:Cachexia / Q000097:blood* / Q000209:etiology / Q000401:mortality; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood / Q000150:complications* / Q000401:mortality; D016019:Survival Analysis; D013806:Theophylline / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015415:Biomarkers; C508600:IL6 protein, human; D015850:Interleukin-6; D020738:Leptin; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D013806:Theophylline; C021183:1,7-dimethylxanthine