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 - 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 -