title: Plasma growth differentiation factor 15 is associated with weight loss and mortality in cancer patients.
abstract: BACKGROUND
  Cancer-related weight loss is associated with increased inflammation and decreased survival. The novel inflammatory mediator growth differentiation factor (GDF)15 is associated with poor prognosis in cancer but its role in cancer-related weight loss (C-WL) remains unclear. Our objective was to measure GDF15 in plasma samples of cancer subjects and controls and establish its association with other inflammatory markers and clinical outcomes.
  
  
  METHODS
  We measured body weight, appetite, plasma GDF15, and other inflammatory markers in men with cancer-related weight loss (C-WL, n = 58), weight stable patients with cancer (C-WS, n = 72), and non-cancer controls (Co, n = 59) matched by age and pre-illness body mass index. In a subset of patients we also measured handgrip strength, appendicular lean body mass (aLBM), Eastern Cooperative Oncology Group (ECOG), and Karnofsky performance scores.
  
  
  RESULTS
  GDF15, interleukin (IL)-6 and IL-8 were increased in C-WL versus other groups. IL-1 receptor antagonist, IL-4, interferon-gamma, tumour necrosis factor alpha, and vascular endothelial growth factor A were increased in C-WL versus C-WS, and Activin A was significantly downregulated in Co versus other groups. C-WL patients had lower handgrip strength, aLBM, and fat mass, and Eastern Cooperative Oncology Group and Karnofsky performance scores were lower in both cancer groups. GDF15, IL-6, and IL-8 significantly correlated with weight loss; GDF15 negatively correlated with aLBM, handgrip strength, and fat mass. IL-8 and Activin A negatively correlated with aLBM and fat mass. GDF15 and IL-8 predicted survival adjusting for stage and weight change (Cox regression P < 0.001 for both).
  
  
  CONCLUSIONS
  GDF15 and other inflammatory markers are associated with weight loss, decreased aLBM and strength, and poor survival in patients with cancer. GDF15 may serve as a prognostic indicator in cancer patients and is being evaluated as a potential therapeutic target for cancer-related weight loss.
authors.affiliation: AVEO Pharmaceuticals Cambridge, MA, USA.
authors.forename: Lorena
authors.initials: L
authors.lastname: Lerner
authors.affiliation: Department of Medicine, Center for Translational Research on Inflammatory Diseases (CTRID), Michael E DeBakey Veterans Affairs Medical Center Houston, TX, USA ; Dan L. Duncan Cancer Center, Baylor College of Medicine Houston, TX, USA.
authors.forename: Teresa G
authors.initials: TG
authors.lastname: Hayes
authors.affiliation: AVEO Pharmaceuticals Cambridge, MA, USA.
authors.forename: Nianjun
authors.initials: N
authors.lastname: Tao
authors.affiliation: AVEO Pharmaceuticals Cambridge, MA, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Krieger
authors.affiliation: AVEO Pharmaceuticals Cambridge, MA, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Feng
authors.affiliation: AVEO Pharmaceuticals Cambridge, MA, USA.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Wu
authors.affiliation: AVEO Pharmaceuticals Cambridge, MA, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Nicoletti
authors.affiliation: AVEO Pharmaceuticals Cambridge, MA, USA.
authors.forename: M Isabel
authors.initials: MI
authors.lastname: Chiu
authors.affiliation: AVEO Pharmaceuticals Cambridge, MA, USA.
authors.forename: Jeno
authors.initials: J
authors.lastname: Gyuris
authors.affiliation: Department of Medicine, Center for Translational Research on Inflammatory Diseases (CTRID), Michael E DeBakey Veterans Affairs Medical Center Houston, TX, USA ; Dan L. Duncan Cancer Center, Baylor College of Medicine Houston, TX, USA ; Department of Molecular and Cell Biology and Huffington Center on Aging, Baylor College of Medicine Houston, TX, USA.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Garcia
keywords: Activin A; Cachexia; Cytokines; GDF15; IL-6; IL-8; Inflammation; MIC-1