Circulating monocyte chemoattractant protein‐1 (MCP‐1) is associated with cachexia in treatment‐naïve pancreatic cancer patients

• Type of Material: Article
• Authors: Erin E. Talbert, Ohio State University; Heather L. Lewis, Ohio State University; Matthew R. Farren, Emory University; Mitchell L. Ramsey, Ohio State University; Jeffery M. Chakedis, Ohio State University; Priyani Rajasekera, Ohio State University; Ericka Haverick, Ohio State University; Angela Sarna, Ohio State University; Mark Bloomston, 21st Century Oncology, Inc.; Timothy M. Pawlik, Ohio State University; Teresa A. Zimmers, Indiana University School of Medicine; Gregory Lesinski, Emory University; Phil A. Hart, Ohio State University; Mary E. Dillhoff, Ohio State University; Carl R. Schmidt, Ohio State University; Denis C. Guttridge, Ohio State University
• Language: English
• Date: 2018-04-01
• Publisher: Wiley Open Access: Various Creative Commons Licenses
• Publication Version: Final Published Version
• Copyright Statement: © 2018 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1002/jcsm.12251
• Title of Journal or Parent Work: Journal of Cachexia, Sarcopenia and Muscle
• ISSN: 2190-5991
• Volume: 9
• Issue: 2
• Start Page: 358
• End Page: 368
• Grant/Funding Information: E.E.T. was supported both through a Weiss Postdoctoral Fellowship and an American Cancer Society Postdoctoral Fellowship (PF‐15‐156‐01‐CSM).; Additional support was provided by the Ohio State University Comprehensive Cancer Center Cachexia Group.; Support for this study was provided through The National Institutes of Health R01 CA180057 (D.C.G.), T32CA106196 (E.E.T.), and T32CA090223 (M.R.F.).
• Keywords: Life Sciences & Biomedicine; OBESITY; Geriatrics & Gerontology; HEIGHT; MACROPHAGE INFILTRATION; Medicine, General & Internal; SELF-REPORTED WEIGHT; Wasting; Weight loss; INSULIN-RESISTANCE; Science & Technology; TYPE-2 DIABETES-MELLITUS; BODY-MASS INDEX; ADIPOSE-TISSUE; INFLAMMATION; PHYSICAL-ACTIVITY; General & Internal Medicine; Biomarker
• Research Categories: Health Sciences, General; Health Sciences, Oncology

Abstract

Cancer-associated wasting, termed cancer cachexia, has a profound effect on the morbidity and mortality of cancer patients but remains difficult to recognize and diagnose. While increases in circulating levels of a number of inflammatory cytokines have been associated with cancer cachexia, these associations were generally made in patients with advanced disease and thus may be associated with disease progression rather than directly with the cachexia syndrome. Thus, we sought to assess potential biomarkers of cancer-induced cachexia in patients with earlier stages of disease. Methods: A custom multiplex array was used to measure circulating levels of 25 soluble factors from 70 pancreatic cancer patients undergoing attempted tumour resections. A high-sensitivity multiplex was used for increased sensitivity for nine cytokines. Results: Resectable pancreatic cancer patients with cachexia had low levels of canonical pro-inflammatory cytokines including interleukin-6 (IL-6), interleukin-1β (IL-1β), interferon-γ (IFN-γ), and tumour necrosis factor (TNF). Even in our more sensitive analysis, these cytokines were not associated with cancer cachexia. Of the 25 circulating factors tested, only monocyte chemoattractant protein-1 (MCP-1) was increased in treatment-naïve cachectic patients compared with weight stable patients and identified as a potential biomarker for cancer cachexia. Although circulating levels of leptin and granulocyte-macrophage colony-stimulating factor (GM-CSF) were found to be decreased in the same cohort of treatment-naïve cachectic patients, these factors were closely associated with body mass index, limiting their utility as cancer cachexia biomarkers. Conclusions: Unlike in advanced disease, it is possible that cachexia in patients with resectable pancreatic cancer is not associated with high levels of classical markers of systemic inflammation. However, cachectic, treatment-naïve patients have higher levels of MCP-1, suggesting that MCP-1 may be useful as a biomarker of cancer cachexia.