TY - JOUR
T1 - Circulating interleukin-6 is associated with disease progression, but not cachexia in pancreatic cancer
AU - Ramsey, Mitchell L.
AU - Talbert, Erin
AU - Ahn, Daniel
AU - Bekaii-Saab, Tanios
AU - Badi, Niharika
AU - Bloomston, P. Mark
AU - Conwell, Darwin L.
AU - Cruz-Monserrate, Zobeida
AU - Dillhoff, Mary
AU - Farren, Matthew R.
AU - Hinton, Alice
AU - Krishna, Somashekar G.
AU - Lesinski, Gregory B.
AU - Mace, Thomas
AU - Manilchuk, Andrei
AU - Noonan, Anne
AU - Pawlik, Timothy M.
AU - Rajasekera, Priyani V.
AU - Schmidt, Carl
AU - Guttridge, Denis
AU - Hart, Phil A.
N1 - 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
PY - 2019/1
Y1 - 2019/1
N2 - 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.
AB - 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.
KW - Biomarker
KW - Inflammation
KW - Pancreatic ductal adenocarcinoma
KW - Weight loss
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U2 - 10.1016/j.pan.2018.11.002
DO - 10.1016/j.pan.2018.11.002
M3 - Article
C2 - 30497874
AN - SCOPUS:85057259564
SN - 1424-3903
VL - 19
SP - 80
EP - 87
JO - Pancreatology
JF - Pancreatology
IS - 1
ER -