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 journalArticle

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

Keywords

  • Biomarker
  • Inflammation
  • Pancreatic ductal adenocarcinoma
  • Weight loss

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Gastroenterology

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    Ramsey, M. L., Talbert, E., Ahn, D., Bekaii-Saab, T., Badi, N., Bloomston, P. M., Conwell, D. L., Cruz-Monserrate, Z., Dillhoff, M., Farren, M. R., Hinton, A., Krishna, S. G., Lesinski, G. B., Mace, T., Manilchuk, A., Noonan, A., Pawlik, T. M., Rajasekera, P. V., Schmidt, C., ... Hart, P. A. (2019). Circulating interleukin-6 is associated with disease progression, but not cachexia in pancreatic cancer. Pancreatology, 19(1), 80-87. https://doi.org/10.1016/j.pan.2018.11.002