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. 2015 Dec;6(4):317-24.
doi: 10.1002/jcsm.12033. Epub 2015 Apr 30.

Plasma growth differentiation factor 15 is associated with weight loss and mortality in cancer patients

Lorena Lerner  1 , Teresa G Hayes  2 , Nianjun Tao  1 , Brian Krieger  1 , Bin Feng  1 , Zhenhua Wu  1 , Richard Nicoletti  1 , M Isabel Chiu  1 , Jeno Gyuris  1 , Jose M Garcia  3
Affiliations

Plasma growth differentiation factor 15 is associated with weight loss and mortality in cancer patients

Lorena Lerner et al. J Cachexia Sarcopenia Muscle. 2015 Dec.

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).

Conclusion: 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.

Keywords: Activin A; Cachexia; Cytokines; GDF15; IL-6; IL-8; Inflammation; MIC-1.

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Figures

Figure 1
Figure 1
Upregulated cytokine levels in weight losing patients with cancer. Data are represented as box plots (median and quartiles). Circulating levels of cytokines in control patients (Co), weight stable cancer patients (C-WS), and weight losing cancer patients (C-WL). Non-parametric one-way ANOVA Kruskal–Wallis test and multiple comparisons test Dunn’s *P < 0.05, **P < 0.01, ***P < 0.001.
Figure 2
Figure 2
Kaplan–Meier survival curves according to GDF15 quartiles (ng/mL, A) and to IL-8 quartiles (pg/mL, B).
See this image and copyright information in PMC

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