Association between Growth Differentiation Factor-15 (GDF-15) Serum Levels, Anorexia and Low Muscle Mass among Cancer Patients

SIMPLE SUMMARY: In our study, the novel inflammatory cytokine Growth Differentiation Factor-15 (GDF-15) has been found elevated in patients with gastrointestinal and lung cancer and associated with anorexia. Patients with gastrointestinal cancer were found more anorexic (based on the FAACT score) and showed higher GDF-15 serum levels than patients with lung cancer. We also evaluated the muscularity status of the patients by CT scan. No difference was found in GDF-15 levels between cancer patients with low muscle mass vs. those with moderate/high muscularity and between patients with body weight loss vs. those with stable weight. Based on our observations, we confirm the role of GDF-15 in the pathogenesis of anorexia in cancer, although the mechanisms of action of this cytokine in cancer should be further unveiled also regarding its potential involvement in changes in muscularity. ABSTRACT: The pathophysiology of cancer anorexia is complex and serum biomarkers, including growth and differentiation factor(s) (GDF), may be modulated. We explored the association(s) between GDF-15 serum levels and anorexia and, secondarily, with low muscle mass and body weight loss in cancer patients. We considered gastrointestinal and lung cancer patients (CP) and healthy BMI-matched controls. The FAACT-questionnaire was administered to diagnose anorexia and we calculated the L3-SMI by CT scan to assess low muscularity, setting their cutoff values at the lowest tertile. GDF-15 serum levels were assessed by ELISA. We enrolled 59 CP and 30 controls; among CP, 25 were affected by gastrointestinal and 34 by lung cancer. Anorexia was present in 36% of CP. Gastrointestinal CP resulted more anorexic compared to lung CP (p = 0.0067). Low muscle mass was present in 33.9% of CP and L3-SMI was lower in gastrointestinal compared to lung CP (p = 0.049). The GDF-15 levels were higher in CP vs. controls (p = 0.00016), as well as in anorexic vs. non-anorexic CP (p = 0.005) and vs. controls (p < 0.0001). Gastrointestinal CP showed higher GDF-15 levels vs. lung CP (p = 0.0004). No difference was found in GDF-15 between CP with low muscle mass and those with moderate/high muscularity and between patients with body weight loss and those with stable weight. Our data support the involvement of GDF-15 in the pathogenesis of cancer anorexia. The mechanisms of action of GDF-15 in cancer should be further clarified also regarding the changes in muscularity.