MPTH-28. ACID CERAMIDASE IS A SUPPLEMENTARY BIOMARKER OF SURVIVAL IN GLIOMA

Abstract

BACKGROUND: Acid ceramidase (ASAH1) plays a significant role in tumor progression and invasion, but the exact role of ASAH1 in glioma biology is still being established. METHODS: All studies were IRB-approved. Tissue specimens from consented patients who previously underwent therapeutic brain tumor resection were submitted for immunohistochemical (IHC) and molecular testing. Additionally, 15 banked glioblastoma (GBM) specimens were analyzed independently using Western blot and a mass-spectrometrybased proteomics approach. RESULTS: The IHC and molecular information of 19 patients have been analyzed. Patients were divided into two groups based on above/below mean overall survival (OS) for analysis. Group A (high OS) comprised seven Grade II gliomas (four oligodendrogliomas, one astrocytoma, two mixed oligoastrocytomas), and one Grade III mixed oligoastrocytoma. Group B (low OS) included two conventional GBMs, three recurrent GBMs, four GBMs with oligodendroglial component, and two Grade III astrocytomas. Group A had a significantly lower mitotic index than group B (p<0.001), which supports our previously reported differences in ADC and standardized rCBV (sRCBV) between astrocytic and oligodendroglial tumors on advanced MRI. Mass-spectrometry identified ASAH1 among 601 biomarkers studied and demonstrated that a higher expression level of ASAH1 was associated with lower OS. This was confirmed by Western blot analysis. Subsequently, we assessed ASAH1 IHC in our 19 clinical specimens. Group A had a significantly lower mean IHC score than Group B (p=0.012). In agreement, median progression-free survival and OS were significantly higher in Group A than in Group B (p=0.004 and p<0.001, respectively). This is consistent with our previous findings that patients with higher preoperative sRCBV progressed sooner than patients with lower preoperative sRCBV. Other outcome predictors (IDH-1 mutation, 1p19q co-deletion, MGMT methylation) were quite heterogeneous in both groups. Further analysis on these markers, and more specimens, is underway. CONCLUSION: We propose ASAH1 as a potential supplementary survival marker in glioma.