Association of Cachexia and Body Composition With Circulating Growth Differentiation Factor-15 (Gdf-15) Serum Levels in Patients With Gastric and Colorectal Cancer

Cancer-associated cachexia remains a primary focus of clinical research, with increasing attention on molecular targets such as Growth Differentiation Factor 15 (GDF-15). A recent Phase 2 trial showed that GDF-15 inhibition via ponsegromab improved body weight and physical activity, reinforcing its role as a key driver. While other targets are in development, evidence linking GDF-15 to muscle mass remains inconclusive, and gastric and colorectal cancers are underrepresented in these clinical studies. This landscape underscores the need to investigate the clinical implications of elevated GDF-15 levels across specific oncological populations. To investigate associations between body composition, radiodensity, and adipose tissue glucose uptake (via PET/CT) with plasma GDF-15 levels in gastric and colorectal cancer patients. This prospective study included patients with gastric/gastroesophageal junction (GEJ) adenocarcinoma (n=67; 42 analyzed for GDF-15) and colorectal cancer (n=46; 38 analyzed for GDF-15). Data were managed via REDCap. Preoperative serum was analyzed for GDF-15 using Luminex®. Body composition was assessed by CT; cachexia followed GLIM (gastric) or Fearon (colorectal) criteria. Statistical analysis in Jamovi 2.3 included Shapiro-Wilk, × 2, Student’s t/Mann-Whitney U, and Spearman’s rank correlation (p1000 pg/mL (230 ± 35 vs. 136 ± 72, p = 0.017). No association was found with PET/CT uptake in VAT (p=0.774) or SAT (p=0.518). GDF-15 was associated with cachexia and musculoskeletal impairment in gastric cancer, and with weight loss and visceral adiposity in colorectal cancer. The lack of correlation with PET/CT glucose uptake suggests GDF-15 influences tissue wasting independent of glucose metabolic alterations in these settings. These results highlight GDF-15 as a potential target for personalized therapeutic interventions in gastrointestinal oncology.