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Pancreatology. 2019 Jan;19(1):80-87. doi: 10.1016/j.pan.2018.11.002. Epub 2018 Nov 10.

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

Author information

1
Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
2
Department of Cancer Biology and Genetics and The Ohio State University Comprehensive Cancer Center Cachexia Program, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
3
Division of Hematology/Medical Oncology, Mayo Clinic, Phoenix, AZ, USA.
4
Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH, USA; Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
5
21st Century Oncology, Inc., Fort Meyers, FL, USA.
6
Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
7
Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA.
8
Division of Biostatistics, The Ohio State University, Columbus, OH, USA.
9
Division of Medical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
10
Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH, USA. Electronic address: philip.hart@osumc.edu.

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

PMID:
30497874
DOI:
10.1016/j.pan.2018.11.002

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