Abstract 3504: Plasma growth differentiating factor-15 (GDF-15) and other inflammatory markers are associated with weight loss and poor prognosis in cancer patients.

Abstract

Abstract Background: Cachexia is associated with increased inflammatory markers and decreased survival in cancer. Also, elevated GDF-15 has been associated with poor prognosis in several cancer types but its role in cachexia is not well-understood. Methods: We measured body weight change, appetite, plasma GDF-15, and other inflammatory markers in 62 males with cancer-cachexia (CC), 72 non-cachectic cancer subjects (CNC) and 64 non-cancer controls (Co) matched by age, gender and pre-illness body weight. In a subset of patients we also measured grip strength (HGS), appendicular lean body mass (aLBM), ECOG and KPS. Results: GDF-15, IL-6 and IL-8 were increased in CC vs. other groups. Activin and G-CSF were significantly upregulated in CC vs. Co. A subset analyses showed that GDF-15, Activin A and IL-8 were increased in CC vs. CNC in lung cancer patients and that GDF-15, IL-6 and IL-8 were increased in CC patients treated with platinum-based chemotherapy. GDF15, IL-6 and IL-8 levels significantly correlated with 6-month weight loss and with IL-6, IL-1ra, IL-2, IL-4, IL-9, IL-10, IFN, MCP-10, MIP-1a, MIP-1b, TNF-a, VGEF and activin in cancer patients. Analysis in a subset of patients showed that CC had lower grip strength, aLBM, and fat mass; and that ECOG and KPS were lower in CC and CNC compared to controls. GDF-15 and IL-8 correlated negatively with aLBM, HGS and fat mass. Activin correlated negatively with aLBM. Survival analysis showed that GDF-15 and IL-8 predicted survival adjusting for stage and weight change (Cox regression p<0.01, HR 3). Conclusion: GDF-15 and other inflammatory markers are associated with weight loss, decreased muscle mass and strength and poor survival in cancer patients. GDF-15 may serve as a prognostic indicator in cancer patients and be a novel therapeutic target for cancer cachexia. Citation Format: Lerner Lorena, Teresa Hayes, Nianjun Tao, Brian Krieger, Bin Feng, Richard Nicoletti, Ailin Bai, Zhigang Weng, Qing Liu, Maria Isabel Chiu, Jeno Gyuris, Jose M. Garcia. Plasma growth differentiating factor-15 (GDF-15) and other inflammatory markers are associated with weight loss and poor prognosis in cancer patients. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3504. doi:10.1158/1538-7445.AM2013-3504