STEM-21. DETERMINATION OF RACIAL DISPARITIES IN GLIOMA THROUGH RAP1B/NOTCH -INDUCED TUMORIGENESIS AND STEMNESS

Abstract

Abstract BACKGROUND The incidence of GBM and survival rates after diagnosis vary significantly by race, with Caucasian Americans (CAs) having higher incidence and lower survival rates than African Americans (AAs). Accumulating evidence suggests that the failure of current therapies is partly attributed to the presence of glioma stem cells (GSC), leading to tumor progression and recurrence. Our recent work demonstrates that Ras-associated protein 1 (Rap1), a Ras-like small GTP-binding protein superfamily member, has roles in glioma cell proliferation and invasion. METHODS 1) The TCGA database was analyzed to investigate the predictive role of Rap1b in glioma patients. 2) The immunohistochemical staining for Rap1b1 was performed using the rabbit polyclonal anti-Rap1b in glioma tissue microarrays (TMA) from 76 glioma patients with 10 normal individuals. The staining intensity of cells in TMA was evaluated in three different bright fields (≥100 cells/field). The semi-quantitative HSCORE was calculated for Rap1b. 3) The mechanism of the oncogenic role of Rap1b in glioma was examined using in vitro cell culture. RESULTS 1. TCGA data showed that Rap1b mRNA is highly expressed in GBM patients compared to normal controls, indicating that Rap1b is a potential oncotarget in GBM. Expression of Rap1b is associated with worse survival in glioma patients, especially in CAs, but not in AAs. 2. The TMA data showed that elevated Rap1b protein expression correlates with grades in glioma patients. 3. In vitro studies showed that GSCs exhibit high levels of Rap1b, silencing Rap1b decreases glioma cell growth and invasion through G1/S arrest and the induction of apoptosis, as well as reduces Notch1 signaling in glioma cells; while potentiates GBM cell response to TMZ. CONCLUSION This study provided new knowledge of Rap1b’s potential as a therapeutic drug target for GBM therapy and revealed biological diversity across races and unaddressed health disparities.