Plasma growth differentiation factor 15 is associated with weight loss and mortality in cancer patients: GDF15 in cancer-related weight loss
Open accessAbstract
BACKGROUND: Cancer-related weight loss is associated with increased inflammation and decreased survival. The novel inflammatory mediator growth differentiation factor (GDF)15 is associated with poor prognosis in cancer but its role in cancer-related weight loss (C-WL) remains unclear. Our objective was to measure GDF15 in plasma samples of cancer subjects and controls and establish its association with other inflammatory markers and clinical outcomes. METHODS: We measured body weight, appetite, plasma GDF15, and other inflammatory markers in men with cancer-related weight loss (C-WL, n = 58), weight stable patients with cancer (C-WS, n = 72), and non-cancer controls (Co, n = 59) matched by age and pre-illness body mass index. In a subset of patients we also measured handgrip strength, appendicular lean body mass (aLBM), Eastern Cooperative Oncology Group (ECOG), and Karnofsky performance scores. RESULTS: GDF15, interleukin (IL)-6 and IL-8 were increased in C-WL versus other groups. IL-1 receptor antagonist, IL-4, interferon-gamma, tumour necrosis factor alpha, and vascular endothelial growth factor A were increased in C-WL versus C-WS, and Activin A was significantly downregulated in Co versus other groups. C-WL patients had lower handgrip strength, aLBM, and fat mass, and Eastern Cooperative Oncology Group and Karnofsky performance scores were lower in both cancer groups. GDF15, IL-6, and IL-8 significantly correlated with weight loss; GDF15 negatively correlated with aLBM, handgrip strength, and fat mass. IL-8 and Activin A negatively correlated with aLBM and fat mass. GDF15 and IL-8 predicted survival adjusting for stage and weight change (Cox regression P < 0.001 for both). CONCLUSION: GDF15 and other inflammatory markers are associated with weight loss, decreased aLBM and strength, and poor survival in patients with cancer. GDF15 may serve as a prognostic indicator in cancer patients and is being evaluated as a potential therapeutic target for cancer-related weight loss.
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Elevated GDF-15 expression and circulating levels correlate with further weight loss and reduced food intake and appetite.
“In addition, elevated GDF-15 expression and circulating levels correlate with further weight loss, reduce food intake and appetite (42, 43, 106).”
From GDF-15 as a Weight Watcher for Diabetic and Non-Diabetic People Treated With Metformin (2020) · cites this paper as [43]
GDF-15 reduces food intake and body weight.
“This gut-brain cytokine works as a prominent player in reducing food intake and body weight in health and disease, like anorexia nervosa and cancer.”
From GDF-15 as a Weight Watcher for Diabetic and Non-Diabetic People Treated With Metformin (2020) · cites this paper as [43]
Higher circulating GDF-15 levels are significantly associated with weight loss in cancer patients.
“Higher circulating GDF-15 levels have been proven to be significantly associated with weight loss in cancer patients (42, 43).”
From GDF-15 as a Weight Watcher for Diabetic and Non-Diabetic People Treated With Metformin (2020) · cites this paper as [43]
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- Authors
- Lerner, L., Hayes, T. G., Tao, N., Krieger, B., Feng, B., Wu, Z., Nicoletti, R., Chiu, M. I., Gyuris, J., & Garcia, J. M.
- Affiliations
- AVEO Oncology (United States) (US)
- Michael E. DeBakey VA Medical Center (US)
- AVEO Pharmaceuticals; Cambridge MA USA
- Department of Medicine, Center for Translational Research on Inflammatory Diseases (CTRID); Michael E DeBakey Veterans Affairs Medical Center; Houston TX USA
- Venue
- Journal of Cachexia Sarcopenia and Muscle
- Publisher
- Wiley
- Published
- 2015-04-30
- Volume
- 6
- Issue
- 4
- Pages
- 317-324
- ISSN
- 2190-5991 (ISSN-L)
- PMC
- PMC4670740
- OpenAlex
- W1556530806
- Cited by
- 208
- References
- 33
- Citations by year
- 2026: 26 · 2025: 22 · 2024: 25 · 2023: 20 · 2022: 29 · 2021: 16 · 2020: 25 · 2019: 19 · 2018: 12 · 2017: 11 · 2016: 3
- FWCI
- 7.28
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Cachexia Sarcopenia and Muscle (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- the Department of Veterans Affairs (I01-BX000507, I01 CX000174)
- National Institutes of Health (AG040583)
- Topics
- Health Sciences › Medicine › Rheumatology › GDF15 and Related Biomarkers
- Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
- Health Sciences › Medicine › Oncology › Inflammatory Biomarkers in Disease Prognosis
- Keywords
- growth differentiation factor 15, cancer-related weight loss, cancer cachexia, inflammation, prognostic factors, interleukin-6, interleukin-8, activin A, grip strength, survival, performance status, plasma biomarkers
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