Circulating interleukin-6 is associated with disease progression, but not cachexia in pancreatic cancer

Mitchell L. Ramsey, Erin Talbert, Daniel Ahn, Tanios Bekaii-Saab, Niharika Badi, P. Mark Bloomston, Darwin L. Conwell, Zobeida Cruz-Monserrate, Mary Dillhoff, Matthew R. Farren, Alice Hinton, Somashekar G. Krishna, Gregory B. Lesinski, Thomas Mace, Andrei Manilchuk, Anne Noonan, Timothy M. Pawlik, Priyani V. Rajasekera, Carl Schmidt, Denis GuttridgePhil A. Hart

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Background: Cachexia is a wasting syndrome characterized by involuntary loss of >5% body weight due to depletion of adipose and skeletal muscle mass. In cancer, the pro-inflammatory cytokine interleukin-6 (IL-6) is considered a mediator of cachexia and a potential biomarker, but the relationship between IL-6, weight loss, and cancer stage is unknown. In this study we sought to evaluate IL-6 as a biomarker of cancer cachexia while accounting for disease progression. Methods: We retrospectively studied 136 subjects with biopsy-proven pancreatic ductal adenocarcinoma (PDAC), considering the high prevalence of cachexia is this population. Clinical data were abstracted from subjects in all cancer stages, and plasma IL-6 levels were measured using a multiplex array and a more sensitive ELISA. Data were evaluated with univariate comparisons, including Kaplan-Meier survival curves, and multivariate Cox survival models. Results: On multiplex, a total of 43 (31.4%) subjects had detectable levels of plasma IL-6, while by ELISA all subjects had detectable IL-6 levels. We found that increased plasma IL-6 levels, defined as detectable for multiplex and greater than median for ELISA, were not associated with weight loss at diagnosis, but rather with the presence of metastasis (p < 0.001 for multiplex and p = 0.007 for ELISA). Further, while >5% weight loss was not associated with worse survival, increased plasma IL-6 by either methodology was. Conclusion: Circulating IL-6 levels do not correlate with cachexia (when defined by weight loss), but rather with advanced cancer stage. This suggests that IL-6 may mediate wasting, but should not be considered a diagnostic biomarker for PDAC-induced cachexia.

Original languageEnglish
Pages (from-to)80-87
Number of pages8
JournalPancreatology
Volume19
Issue number1
DOIs
StatePublished - Jan 2019

Bibliographical note

Funding Information:
Research reported in this publication was supported by the National Cancer Institute (NCI) and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) under award number U01DK108327 (DC, PH), NCI through R01CA180057 (DG) and 5T32CA090223-13 (MF). ET was supported by an American Cancer Society Postdoctoral Fellowship (PF-15-156-01-CSM). Additional funding was provided by The Ohio State University Comprehensive Cancer Center (DG) and ChiRhoClin Research Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Funding Information:
Research reported in this publication was supported by the National Cancer Institute (NCI) and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) under award number U01DK108327 (DC, PH), NCI through R01CA180057 (DG) and 5T32CA090223-13 (MF). ET was supported by an American Cancer Society Postdoctoral Fellowship ( PF-15-156-01-CSM ). Additional funding was provided by The Ohio State University Comprehensive Cancer Center (DG) and ChiRhoClin Research Institute . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Publisher Copyright:
© 2018 IAP and EPC

Keywords

  • Biomarker
  • Inflammation
  • Pancreatic ductal adenocarcinoma
  • Weight loss

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Gastroenterology

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