Abstract B032: Cancer cachexia marker, Growth Differentiation Factor 15 (GDF-15), serum level mapping in real world samples from patients with pancreatic (PANC) or colorectal cancer (CRC)

Abstract Background GDF-15 is an inflammatory cytokine involved in cellular response to stress. Elevated GDF-15 levels are found in patients with cancer and are associated with cachexia, a multifactorial syndrome that co-occurs with various tumor types, characterized by involuntary weight loss and loss of skeletal muscle, leading to fatigue, functional impairment, increased treatment-related toxicity, poor quality of life, and reduced survival. GDF-15 has emerged as a target for cancer cachexia. Here, the GDF-15 levels in real-world clinical samples from patients with CRC or PANC are compared with a range of demographic and clinical parameters. Methods GDF-15 levels were measured in serum collected from adult patients undergoing standard-of-care treatment for either PANC or CRC. Patients were not receiving an anti-GDF-15 therapeutic. Samples were stored in a biobank with associated metadata until this analysis. Serum GDF-15 was quantified using a validated electrochemiluminescence immunoassay and parameters were analyzed using summary statistics. Cachexia status was unknown in all but two cases. Results The sample population (n=100 from USA [n=83], Ukraine [n=17]) included patients with a clinical diagnosis of CRC (56%) or PANC (44%) aged 42 years to >90 years (median: 67); 54% male, 44% female (2% unavailable). As for standard-of-care treatments 70% had systemic therapy (30% unknown), of those, 50% received platinum-based treatment; 3% had radiation (97% unknown), and 8% had surgery (92% unknown). The GDF-15 range in CRC was 490 to >57600pg/mL, with a median that increased by stage across stages: I/II: 1470pg/mL (12.5%), III: 2110pg/mL (55.4%), and IV: 3090pg/mL (23.2%). Males had a higher median GDF-15 (2575pg/mL [57.1%] vs females (1870pg/mL [39.3%]) as well as smokers (median 3070pg/mL [16.1%] vs. non-smokers median 2145pg/mL [35.7%]). The GDF-15 range in PANC was 446 to 22600pg/mL, with a median GDF-15 that was higher in patients with Stage IV disease (5470pg/mL [40.9%]) compared to Stage I/II (3415pg/mL [31.8%], or Stage III 1390pg/mL [15.9%]. Higher median GDF-15 was found in non-smokers (5010pg/mL [47.7%] vs. smokers 1945pg/mL [27.3%]), and in males (4755pg/mL [50%] vs. females 2235pg/mL [50%]). Overall, GDF-15 levels moderately correlated with age (Pearson correlation coefficient: 0.3, natural log scale; p-value= 0.0028). As expected, higher GDF-15 levels were reported in patients with co-morbidities like thalassemia, Parkinson’s and cardiovascular conditions. Conclusions In this real-world analysis, in CRC and PANC, positive correlations were found between increasing GDF-15 serum levels and age, and stage progression. Higher GDF-15 correlated with male sex but smoking status yielded conflicting results. A limited dataset was used therefore results should be interpreted with caution. More analyses of GDF-15 in real-world settings like these are needed to inform development of anti-GDF-15 cachexia treatments. Citation Format: Rowida Abdelgalel, Suga Subramaniam, Tripti Gaur, Victoria Mountain, Bo Jin, Hijung Cho, Claudia Lebedinsky. Cancer cachexia marker, Growth Differentiation Factor 15 (GDF-15), serum level mapping in real world samples from patients with pancreatic (PANC) or colorectal cancer (CRC) [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2025 Oct 22-26; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2025;24(10 Suppl):Abstract nr B032.