Growth differentiating factor-15 (GDF-15): A potential biomarker and therapeutic target for cancer-associated weight loss

Lerner,Lorena; Gyuris,Jeno; Nicoletti,Richard; Gifford,James; Krieger,Brian; Jatoi,Aminah

doi:10.3892/ol.2016.5183

Growth differentiating factor-15 (GDF-15): A potential biomarker and therapeutic target for cancer-associated weight loss

Authors:
- Lorena Lerner
- Jeno Gyuris
- Richard Nicoletti
- James Gifford
- Brian Krieger
- Aminah Jatoi
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Affiliations: AVEO Pharmaceuticals, Cambridge, MA 02142, USA, Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA
Published online on: September 23, 2016 https://doi.org/10.3892/ol.2016.5183
Pages: 4219-4223

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Abstract

Growth differentiating factor-15 (GDF-15), also known as macrophage inhibiting factor‑1, is a member of the transforming growth factor‑β superfamily, which has been implicated in cancer‑associated weight loss. The present study investigated the association between cancer‑associated weight loss and plasma GDF-15 concentration, as well as other biomarkers, in patients with metastatic lung or exocrine pancreatic cancer. A total of 218 patients were enrolled over a 1-year period. The patient cohort included 152 patients with incurable lung cancer and 66 patients with incurable pancreatic cancer. Of the 218 patients, 98 (45%) reported >5% weight loss, 62 (28%) reported ≤5% weight loss and 58 (27%) reported no weight loss in the 6 months prior to diagnosis. In lung cancer patients, higher circulating GDF‑15 levels were significantly associated with weight loss; lung cancer patients who reported >5% weight loss (n=56) were found to exhibit twice the circulating concentration of GDF‑15 compared with those that exhibited no weight loss (n=48) (P<0.0001). Additional mediators, including Activin A, interleukin (IL)‑12, vascular endothelial growth factor A, IL‑1 receptor α, eotaxin and platelet derived growth factor‑BB, were also associated with weight loss; however, the associations were not as strong. In pancreatic cancer patients, no association between GDF‑15 levels and weight loss was identified. However, higher circulating GDF‑15 levels were consistently associated with poor survival in univariate [hazard ratio (HR), 1.13; 95% confidence interval (CI), 1.02‑1.23; P=0.016] and multivariate [HR, 1.1; 95% CI, 1.02-1.24; P=0.03] analysis, respectively. Thus, GDF‑15 requires further study as a biomarker and potential therapeutic target in cancer‑associated weight loss, particularly in lung cancer patients.

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