OP20: DRUGGABLE PROGNOSTIC MARKERS IN PAEDIATRIC EPENDYMOMA; IS BLBP THE SOLUTION?

INTRODUCTION: Paediatric ependymomas are aggressive treatment resistant tumours with a tendency to relapse. This behaviour is consistent with an underlying sub-population of therapy resistant cancer stem cells. Blbp (brain lipid binding protein) is a marker for radial glial cells, the proposed stem cells of origin in ependymoma. PPARs (peroxisome proliferator activated receptors) are transcription factors; two of which (γ and δ) play a key role in modulating the transcriptional activity of Blbp. METHOD: Blbp immunohistochemistry (IHC) staining was performed on patient samples obtained from two trial cohorts; a chemotherapy-led infant trial (CNS 9204) and a radiotherapy-led trial (CNS 9904). Blbp expression in cell lines and stem cell enriched neurospheres was performed using RT-PCR. Viability assays were carried out to assess proliferation and potentiation of response to chemotherapy in 2D & 3D cultures. Cell migration and invasion were assessed by scratch assays and 3-D migration assays respectively. RESULTS: Blbp expression correlated with reduced overall survival (OS) in both trials (CNS9204- 5yr OS 45% vs 80%, P = 0.011 and CNS9904- 5yr OS 38% vs 85%, P = 0.002). 5/5 ependymoma cell lines expressed Blbp which was elevated in stem cell enriched neurospheres. Treatment with three PPAR antagonists diminished Blbp expression and proliferation in 2D and 3D cultures. Cell migration and invasion were also diminished. CONCLUSION: These findings constitute the first conclusive evidence that Blbp is an independent predictor of poor survival in paediatric ependymomas. In addition, treatment with PPAR antagonists may represent an effective novel therapy to prevent invasion in paediatric ependymoma patients.