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

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.