P04.26 * MOLECULAR MECHANISMS OF CIRCULATING MICRORNA BIOMARKERS FOR GLIOBLASTOMA

Abstract

The development of biomarker panels for glioblastoma has the potential to greatly improve the outcome of treatment by assisting in earlier detection, determining response to treatment and predicting prognosis to improve therapeutic strategy. MicroRNAs (miRNAs) present in the circulation of glioblastoma patients provide a relatively non-invasive source of markers for this purpose. Gliomas, including glioblastoma, release miRNAs in exosomes and protein complexes which alter expression levels in the serum of patients. The aim of this study was to isolate and identify deregulated miRNAs from the sera of glioblastoma patients which could be used as biomarkers. Further to this, the molecular mechanisms behind the deregulation of these miRNA biomarkers were also determined. Total RNA was isolated from the sera of glioblastoma patients, patients undergoing elective surgery and volunteers, using phenol-chloroform extraction. Relative expression of miRNAs was determined using qRT-PCR and normalized using a synthetic spike in. Data was analysed using GraphPad Prism 5 software using the delta CT method. Statistical significance was determined using a t-test and one way ANOVA, a p-value of <0.05 was considered significant. Three miRNAs were significantly deregulated in the sera of glioblastoma patients compared to control sera. One prognostic marker determined by Kaplan-meier analysis, one male specific marker and one age-specific marker which could be used as a panel for glioblastoma patients. Further work using glioblastoma tissue will elucidate the role of these miRNAs in glioblastoma including the underlying molecular differences between patients exhibiting deregulated miRNA and subsequently improved prognosis.