Abstract PO-001: Increased growth differentiation factor 15 serum levels in pancreatic cancer patients

Abstract

Abstract Pancreatic cancer has poor outcomes with a 5-year survival rate of 9%. Growth differentiation factor 15 (GDF15) has been shown to play a role in pancreatic cancer progression and tumor growth. It is a stress response cytokine that plays a role in inflammation and cellular metabolism. Signaling via its receptor, glial cell derived neurotropic factor family receptor alpha like (GFRAL), GDF15 influences metabolic homeostasis and immune regulation, which may contribute to favorable energy utilization and immune suppression in pancreatic cancer tumors. We hypothesized that GDF15 levels are associated with pancreatic cancer tumor stage and clinical outcomes. GDF15 levels were measured in human serum from healthy control patients and patients diagnosed with pancreatic cancer. Serum samples and associated clinical data were obtained from an IRB approved institutional repository. In healthy control patients, GDF15 had a mean level of 598 pg/mL (SD +/- 304 pg/mL, n=150). Contrastingly, in a cohort of pancreatic cancer patients across various stages of disease, GDF15 levels were significantly higher with a mean of 2294 pg/mL (SD +/- 2005 pg/mL, n=152) (p-value < 0.0001). GDF15 levels were associated with pancreatic cancer stage (p-value = 0.1824, n=150). GDF15 levels were compared for a subset of pancreatic cancer patients who underwent surgical resection; there was a trend for increased levels of GDF15 in patients who received neoadjuvant treatment compared to those that did not receive neoadjuvant treatment (P-value = 0.0674, n=106). When GDF15 levels measured at the time of surgical resection were compared among patients that later developed recurrence and those that did not, GDF15 levels trended to be lower in patients who did not develop recurrence (p-value = 0.3004, n=52). Additionally, the mean GDF15 serum levels for surgical resection patients whose survival status was deceased (2392 pg/mL, SD +/- 1947 pg/mL, n=36) compared to those that are still alive (1907 pg/mL, SD +/- 1416 pg/mL, n=70) on the date of last follow-up were higher (p-value = 0.1295). Overall, these results showed that GDF15 is significantly elevated in pancreatic cancer patients compared to healthy control patients. In our cohort there is an associated trend between increased GDF15 and the administration of neoadjuvant chemotherapy treatment, increasing pancreatic cancer stage, recurrence and decreased survival. We appreciated trends with GDF-15 serum levels and clinical outcomes, which need to be further validated in a larger cohort of patients. These results suggest that GDF15 or its receptor, GFRAL, may be effective novel targets for the treatment of pancreatic cancer patients. Citation Format: Veronica R. Placencio-Hickok, Arsen Osipov, Sejal Mehta, Subhash D. Katewa, Jiping Zha, Andrew E. Hendifar. Increased growth differentiation factor 15 serum levels in pancreatic cancer patients [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr PO-001.