Advances in Glioma Proteomics – New Technologies and Approaches
Gliomas are primary tumors of the central nervous system. The enormous cellular and clinical heterogeneity of these tumors make them a clinical challenge for diagnosis and treatment. Genome-wide analysis of these tumors has given information on the underlying mutations while earlier proteomics studies using gel-based or gel-free approaches revealed proteins that help in understanding the pathophysiology of these tumors but their clinical application remains in the waiting. For development of biomarkers, validating select protein panels against a specific clinical question in a targeted approach is required. For this purpose, building high confidence portfolio of tumor-associated differential proteins is the first step. In our efforts towards this objective, we have studied differential membrane proteins of the clinical specimens of Gliomas using LC-MS/MS mass spectrometry and quantitation by iTRAQ. Our results on the differential membrane proteins of glioblastoma multiformme (GBM) - the most common and aggressive of the gliomas, and the analysis of the secretome of GBM cell lines will be presented. Our analysis provides support for many proteins and genes implicated in GBMs and other cancers in earlier reports as well as reveals entirely novel proteins. In an expanded analysis, comparison with differential membrane proteins from Gr II and III gliomas, further reveal proteins that are unique to a particular grade. The potential use of this resource in targeted studies for clinical applications will be discussed.