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

1 Citation (Scopus)

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)
JournalPancreatology
DOIs
StateAccepted/In press - Jan 1 2018

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Cachexia
Pancreatic Neoplasms
Disease Progression
Interleukin-6
Weight Loss
Enzyme-Linked Immunosorbent Assay
Neoplasms
Adenocarcinoma
Biomarkers
Wasting Syndrome
Kaplan-Meier Estimate
Tumor Biomarkers
Proportional Hazards Models
Skeletal Muscle
Body Weight
Cytokines
Neoplasm Metastasis
Biopsy

Keywords

  • Biomarker
  • Inflammation
  • Pancreatic ductal adenocarcinoma
  • Weight loss

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Gastroenterology

Cite this

Circulating interleukin-6 is associated with disease progression, but not cachexia in pancreatic cancer. / Ramsey, Mitchell L.; Talbert, Erin; Ahn, Daniel; Bekaii-Saab, Tanios; Badi, Niharika; Bloomston, P. Mark; Conwell, Darwin L.; Cruz-Monserrate, Zobeida; Dillhoff, Mary; Farren, Matthew R.; Hinton, Alice; Krishna, Somashekar G.; Lesinski, Gregory B.; Mace, Thomas; Manilchuk, Andrei; Noonan, Anne; Pawlik, Timothy M.; Rajasekera, Priyani V.; Schmidt, Carl; Guttridge, Denis; Hart, Phil A.

In: Pancreatology, 01.01.2018.

Research output: Contribution to journalArticle

Ramsey, ML, Talbert, E, Ahn, D, Bekaii-Saab, T, Badi, N, Bloomston, PM, Conwell, DL, Cruz-Monserrate, Z, Dillhoff, M, Farren, MR, Hinton, A, Krishna, SG, Lesinski, GB, Mace, T, Manilchuk, A, Noonan, A, Pawlik, TM, Rajasekera, PV, Schmidt, C, Guttridge, D & Hart, PA 2018, 'Circulating interleukin-6 is associated with disease progression, but not cachexia in pancreatic cancer', Pancreatology. https://doi.org/10.1016/j.pan.2018.11.002
Ramsey, Mitchell L. ; Talbert, Erin ; Ahn, Daniel ; Bekaii-Saab, Tanios ; Badi, Niharika ; Bloomston, P. Mark ; Conwell, Darwin L. ; Cruz-Monserrate, Zobeida ; Dillhoff, Mary ; Farren, Matthew R. ; Hinton, Alice ; Krishna, Somashekar G. ; Lesinski, Gregory B. ; Mace, Thomas ; Manilchuk, Andrei ; Noonan, Anne ; Pawlik, Timothy M. ; Rajasekera, Priyani V. ; Schmidt, Carl ; Guttridge, Denis ; Hart, Phil A. / Circulating interleukin-6 is associated with disease progression, but not cachexia in pancreatic cancer. In: Pancreatology. 2018.
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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.",
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author = "Ramsey, {Mitchell L.} and Erin Talbert and Daniel Ahn and Tanios Bekaii-Saab and Niharika Badi and Bloomston, {P. Mark} and Conwell, {Darwin L.} and Zobeida Cruz-Monserrate and Mary Dillhoff and Farren, {Matthew R.} and Alice Hinton and Krishna, {Somashekar G.} and Lesinski, {Gregory B.} and Thomas Mace and Andrei Manilchuk and Anne Noonan and Pawlik, {Timothy M.} and Rajasekera, {Priyani V.} and Carl Schmidt and Denis Guttridge and Hart, {Phil A.}",
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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.

PY - 2018/1/1

Y1 - 2018/1/1

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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