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 Guttridge; Phil A. Hart

doi:10.1016/j.pan.2018.11.002

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

Internal Medicine

Research output: Contribution to journal › Article › peer-review

17 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 language	English
Pages (from-to)	80-87
Number of pages	8
Journal	Pancreatology
Volume	19
Issue number	1
DOIs	https://doi.org/10.1016/j.pan.2018.11.002
State	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.pan.2018.11.002

Cite this

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

@article{e6e9fbe165864ae7bc2b92d58b5b0f35,

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

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.",

keywords = "Biomarker, Inflammation, Pancreatic ductal adenocarcinoma, Weight loss",

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.}",

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: {\textcopyright} 2018 IAP and EPC",

year = "2019",

month = jan,

doi = "10.1016/j.pan.2018.11.002",

language = "English",

volume = "19",

pages = "80--87",

journal = "Pancreatology",

issn = "1424-3903",

publisher = "Elsevier BV",

number = "1",

}

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 2019, 'Circulating interleukin-6 is associated with disease progression, but not cachexia in pancreatic cancer', Pancreatology, vol. 19, no. 1, pp. 80-87. https://doi.org/10.1016/j.pan.2018.11.002

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

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AN - SCOPUS:85057259564

SN - 1424-3903

VL - 19

SP - 80

EP - 87

JO - Pancreatology

JF - Pancreatology

IS - 1

ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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