title: Identification of neutrophil-derived proteases and angiotensin II as biomarkers of cancer cachexia.
abstract: BACKGROUND
  Cachexia is a metabolic disorder characterised by muscle wasting, diminished response to anti-cancer treatments and poor quality of life. Our objective was to identify blood-based biomarkers of cachexia in advanced cancer patients. Hence, we characterised the plasma cytokine and blood cell mRNA profiles of patients grouped in three cohorts: patients with cachexia, pre-cachexia (no cachexia but high CRP levels: ⩾ 5 mg l⁻¹) and no cachexia (no cachexia and CRP: < 5 mg l⁻¹).
  
  
  METHODS
  A total of 122 newly diagnosed cancer patients with seven cancer types were studied prior to their initial therapy. Plasma levels of 22 cytokines were quantified using the bio-plex technology. mRNAs isolated from whole blood and expression profiles were determined by the chip array technology and Ingenuity Pathway Analysis (IPA) software.
  
  
  RESULTS
  In comparison with non-cachectic individuals, both pre-cachectic and cachectic patients showed an increase (⩾ 1.5-folds) in mRNA expression of neutrophil-derived proteases (NDPs) and significantly elevated angiotensin II (Ang II) (P = 0.005 and P = 0.02, respectively), TGFβ1 (P = 0.042 and P < 0.0001, respectively) and CRP (both P < 0.0001) in the plasma. Moreover, cachectic patients displayed a significant increase in IL-6 (P = 0.005), IL-8 (P = 0.001) and absolute neutrophil counts (P = 0.007).
  
  
  CONCLUSIONS
  Ang II, TGFβ1, CRP and NDP are blood biomarkers for cancer cachexia. These findings contribute to early diagnosis and prevention of cachexia.
authors.affiliation: Goodman Cancer Research Centre, McGill University. Montreal, Canada.|Department of Biochemistry, McGill University. Montreal, Canada.
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Penafuerte
authors.affiliation: Département de médecine familiale et de médecine d'urgence Centre de Recherche sur le Cancer Université Laval, Centre de recherche du CHU de Québec, Québec, Canada.|Division of Clinical Epidemiology McGill University Health Centre, Montreal, Canada.
authors.forename: Bruno
authors.initials: B
authors.lastname: Gagnon
authors.affiliation: Goodman Cancer Research Centre, McGill University. Montreal, Canada.|Department of Biochemistry, McGill University. Montreal, Canada.
authors.forename: Jacinthe
authors.initials: J
authors.lastname: Sirois
authors.affiliation: Division of Clinical Epidemiology McGill University Health Centre, Montreal, Canada.
authors.forename: Jessica
authors.initials: J
authors.lastname: Murphy
authors.affiliation: Professor Emeritus, Department of Oncology, McGill University. Montreal, Canada.|Professor Emeritus, University of Alberta, Edmonton, Canada.
authors.forename: Neil
authors.initials: N
authors.lastname: MacDonald
authors.affiliation: Goodman Cancer Research Centre, McGill University. Montreal, Canada.|Department of Biochemistry, McGill University. Montreal, Canada.
authors.forename: Michel L
authors.initials: ML
authors.lastname: Tremblay
mesh_terms: D000804:Angiotensin II / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D002100:Cachexia / Q000097:blood* / Q000201:enzymology; D016022:Case-Control Studies; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood* / Q000201:enzymology; D009504:Neutrophils / Q000201:enzymology*; D010447:Peptide Hydrolases / Q000097:blood*; D012333:RNA, Messenger / Q000097:blood
chemical_list: D014408:Biomarkers, Tumor; D016207:Cytokines; D012333:RNA, Messenger; D000804:Angiotensin II; D010447:Peptide Hydrolases