BIOM-02. Examination of Growth Differentiation Factor 15 (GDF15) tumor expression as a potential prognostic biomarker in pediatric brain and solid tumors

Background Despite the evolving molecular characterization of pediatric tumors, treatment-related morbidity and mortality remains high. Growth Differentiation Factor 15 (GDF15), an inflammatory cytokine, facilitates tumor angiogenesis, growth, and metastasis in adults, leading to malignant progression, metastasis, and recurrence in gastric cancers and low-grade gliomas. This study is the first evaluation of GDF15 tumor expression in pediatric brain and solid tumors investigating association with prognosis and outcomes. Methods We reviewed precision genomics data for 150 pediatric central nervous system (CNS) and non-CNS solid tumors from our single center. GDF15 RNA expression (normalized to ß-actin) was log-transformed, comparing mean GDF15 expression based on histologic diagnosis, survival, and metastatic or progressive disease. Results Medulloblastoma showed highest mean GDF15 expression (1.96+0.66, N = 3) and Ewing sarcoma showed the lowest (0.12+0.029, N = 18). There was no statistical difference between GDF15 expression in CNS versus solid tumors (p = 0.87). Mean GDF15 expression was higher in progressive versus non-progressive disease (1.35 and 0.83 respectively, p = 0.02), as well as for deceased patients compared to those in active treatment or observation (1.61 and 0.94 respectively, p < 0.01). GDF15 expression was higher in progressive/relapsed tumors compared to diagnosis samples (1.42 and 0.95 respectively, p = 0.03). There was no statistical difference between a single relapse and multiple relapses/progressions (p = 0.60). While not statistically significant, GDF15 expression was higher in metastatic compared to nonmetastatic disease at diagnosis (1.46 and 1.05, p = 0.09). Conclusions We demonstrate GDF15 correlates with metastatic presentation, disease progression, and worse survival. Examining existing pediatric tumor molecular data is feasible and mirrors adult cancer studies showing GDF15 correlates with treatment resistance and worse survival. Ongoing efforts to characterize GDF15 in pediatric tumors are necessary requiring larger, disease-specific pediatric studies (i.e., Children’s Brain Tumor Network database) to elucidate GDF15’s possible role as a disease biomarker or prognostic indicator of childhood cancer morbidity and mortality.