CBMT-12. FATTY ACID SYNTHASE POSITIVE EVs AS NOVEL BIOMARKERS IN BRAIN CANCER

BACKGROUND: Extracellular vesicles (EVs) are known for their important role in cancer progression and hold considerable potential as tumor biomarkers. However, purification of tumor-specific EVs from plasma is still a pressing need since contamination by normal host cell-EVs, results in compromised analytical sensitivity. Fatty acid synthase (FASN) was recently shown by us to be present on EVs from cultured glioma cells. Here we analyzed circulating patient EVs for the expression of FASN, CD9, CD81 and CD63. METHODS: Plasma EVs from patients with glioblastoma (n=24), anaplastic astrocytoma (n=6) and healthy controls (n=16) as well as EVs from early passage glioma stem cells (GSCs) were analyzed for FASN, CD9, CD81, CD63 by imaging flow cytometry (IFC). EVs were further investigated by nanoparticle tracking analysis (NTA), electron microscopy and immunoblotting. Glioblastomas, anaplastic astrocytomas and normal brain tissue specimens were analyzed for FASN by Western blotting and immunohistochemistry. RESULTS: FASN is elevated in glioblastoma tissue compared to noncancerous brain and FASN expression levels correlate with WHO grade (p+/CD81(+)and FASN(+)/CD63(+)EVs are present in plasma from patients with glioblastoma and anaplastic astrocytoma as determined by IFC (p+EVs and double positive (CD9(+)/CD63(+), CD9(+)/CD81(+)or CD63(+)/CD81(+)) EVs (p CONCLUSION: FASN expression is elevated on circulating EVs from patients with malignant gliomas and FASN is a promising marker for the identification and enrichment of glioma-derived plasma EVs, an important prerequisite for in-depth genetic, epigenetic and transcriptional analyses that could inform clinicians on molecular alterations and help monitoring treatment efficacy.