PURPOSE Cancer cachexia is a prevalent condition in pancreatic cancer (PC), affecting up to 80% of patients. There is an urgent need to understand this syndrome and identify potential targetable therapeutic pathways. Given the role of growth differentiation factor-15 (GDF-15) on regulation of energy homeostasis, it has been identified as a potential driver of cancer cachexia. We conducted a study to evaluate serum GDF-15 levels in patients with PC and compare with levels from noncancer patients. We also investigated GDF-15 across several disease characteristics such as stage, resectability status, and neoadjuvant therapy. PATIENTS AND METHODS Patient serum samples were collected from healthy adults without self-reported diseases (n = 150) and patients with histologically confirmed PC (n = 176) between May 2010 and May 2024. Serum GDF-15 levels were measured using a Meso Scale Discovery (MSD)–based GDF-15 assay. The Welch t-test was used to compare GDF-15 measurements from the various cohorts, ordinary one-way analysis of variance for comparison of disease stage, and paired t -test for analysis of serial GDF-15 measurements. RESULTS The mean level GDF-15 for patients with PC was significantly higher at 2,505 pg/mL (SD ± 2,539), compared with 598 pg/mL (SD ± 304) for healthy controls (HCs) ( P < .0001). Patients with advanced unresectable cachectic PC had a significantly higher mean GDF-15 of 3,029 pg/mL (SD ± 3,285; n = 78) relative to resectable patients with PC, 2,088 pg/mL (SD ± 1,633; n = 98; P = .0227). No statistical difference was seen across PC stages 1 through four ( P = .2176). CONCLUSION Our study reports a mean serum level of GDF-15 specifically in patients with PC and demonstrates that GDF-15 is significantly higher compared with HCs. These results reinforce GDF-15 being a potential therapeutic target to address cachexia in patients with PC.
Levi et al. (Mon,) studied this question.