Grant: Operating Grant

Glioblastoma multiforme (GBM) is the most common adult primary brain tumor, with a mean life expectancy of ~12-16 months after diagnosis. The confirmatory diagnosis of GBM from other brain lesions, as well as determination of its molecular phenotype to guide and follow biological therapies, currently requires surgery, with its inherent risks. Serum biomarkers offer the possibility for repetitive non-invasive monitoring of GBMs to complement current radiological and pathological analysis. Our proposal involves collaboration between experts in proteomics, bio-informatics and brain tumor surgeon-scientists. Selection of candidate biomarkers will begin with mass spectrometry based differential proteomic expression analysis of GBMs versus normal brains. Bioinformatic analysis will narrow this anticipated large list of proteins to those which are secreted or shed as potential candidate serum biomarkers. Further verification will involve analysis of these putative biomarkers in the condition media of cultured GBM cell lines. Thus having a finite list of potential biomarkers, we will analyze sera from GBM patients for these proteins using conventional methods and mass spectrometry. To determine specificity of these serum markers to GBM patients we will analyze sera from normal and individuals known to harbor other cancers. The validated serum markers will be evaluated on a large number of GBM specimens using tissue microarrays and correlated to relevant clinical parameters such as survival as well as relevant subgroups of GBMs, which differ in their molecular profile. With this sequential set of studies we will be able to develop a panel of serum biomarkers to aid in the non-invasive diagnosis, prognosis and molecular signature, which will help guide biological therapies and hopefully prognosis of GBM patients.