Abstract 4854: A translational multiplexed hypothesis generating study on circulating cytokines in patients with cancer cachexia
Authors: Mª Teresa Agullo-Ortuño, Virginia Pardo-Marques, Elena Prieto-Garcia, C. Vanesa Diaz-Garcia, Irene Otero, Jose A. Lopez-Martin
Journal: Cancer Research (2019)

Abstract Cancer cachexia is a frequent pathophysiological state associated to terminal stage cancer patients, characterized by a significant reduction in body weight and resistant to nutritional interventions. It is an unmet medical need, and its underlying mechanisms are not completely understood. Objectives: To measure multiple soluble cytokines in patients with cachexia, to develop new hypotheses on pathways and/or eventual therapeutic targets. Methods: This is part of a pilot, observational, cross-sectional, case-control, IRB-reviewed translational research in cancer patients with/without cachexia. Anthropometric, clinical and biochemical data from consenting eligible cancer patients were collected. Blood samples were collected from all the participants, and plasma was separated and immediately stored at -20°C until analysis. For this substudy, human 63-plex kits were purchased from eBiosciences and used according to the manufacturer's recommendations. Plates were read using a Luminex 200 instrument, and the assay was performed in the Human Immune Monitoring Center at Stanford University (CA, USA). Data were analyzed by univariate and multivariate methods, using error adjustments for multiple testings (False Discovery Rate, FDR). A total of 15 subjects were included in this study, 8 cachectic and 7 non-cachectic patients. Median age in cachectic group was 61.5 (36-81) years versus 63.9 (48-80) in non-cachectic group. The respective relative weight loss within the prior 3 months was 17.6% and 1.0%. Clinical, analytical and metabolomics from these patients have been reported elsewhere (doi: 10.1002/jcsm.12270). Of the 63 cytokines tested in our panel, 18 have been selected for fold-change (FC) analysis: for 12, their log2(FC)&amp;gt;1 (IL1RA, ENA78, IL8, GROA, IL23, MCP1, BDNF, PDGFB, IL18, IL21, RESISTIN, IL6), being the FC &amp;gt; 10x for IL1RA, ENA78, IL8, GROA and IL23. For the remaining 6, their log2(FC) &amp;lt; -1 (LEPTIN, GMCSF, IL12P40, IL1B, CD40L, IL5). The cytokines selected for their FDR were: LEPTIN, LIF, GMCSF, RESISTIN, TNFA, IL1B, IL12P40, IL4, IL12p70, BDNF, IL2, IL5, IL23, IL17A and IL13. We integrated these results with prior metabolomics research and performed pathway analyses that enabled us to identify a significant enrichment in several pathways related with infections, immune response, inflammation, energy homeostasis and cancer. This study, despite the size constraints, is able to capture known players in cancer cachexia (leptin, IL6, IL1). We show a potential role for BDNF (brain derived neurotrophic factor), which and has been described as a master coordinator of the physiological mechanisms that regulate food intake and energy expenditure, and identified as a player in murine models for cancer cachexia. Results from this study will be integrated with data from additional research in the same patients (clinical, analytical, metabolomics and proteomics). Citation Format: Mª Teresa Agullo-Ortuño, Virginia Pardo-Marques, Elena Prieto-Garcia, C. Vanesa Diaz-Garcia, Irene Otero, Jose A. Lopez-Martin. A translational multiplexed hypothesis generating study on circulating cytokines in patients with cancer cachexia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4854.