Abstract

Quantitative and Functional Proteomics to Understand Glioma Pathogenesis and Identification of Biomarkers

Sanjeeva Srivastava, Associate Professor, Indian Institute of Technology Bombay

Gliomas are the most lethal form of the solid tumors that are characterized by rapidly proliferating cells frequently associated with an invasive phenotype. Analysis of serum, tissue and CSF samples at proteome level presents different type of complexity associated with these samples and this overwhelming complexity of proteome requires very high-throughput techniques for rapid analysis. Despite the significant advancements in molecular biology tools, this demand has not been satisfied and only a small fraction of the proteome has been understood at the biochemical level. To obtain an in-depth understanding of glioma pathogenesis and identification of biomarkers, we have performed quantitative and functional proteomic studies of different grades of glioma samples by employing 2D-DIGE, Mass Spectrometry and Protein microarrays. In serum proteomic analysis of gliomas we have identified few significant proteins such as haptoglobin, ceruloplasmin, vitamin-D binding protein, which have role in the tumor pathogenesis. We have identified differentially expressed proteins such as SIRT2, GFAP, SOD, CDC42 in different grades of gliomas by performing tissue proteome analysis. The CSF proteomic analysis of low vs. high-grade gliomas revealed role of proteins such as Apolipoprotein E, Dickkopf Related Protein 3 and Serum Albumin in gliomas. The targeted proteomic analysis of JAK-STAT pathway enhanced our understanding of critical role of these proteins in growth and survival of gliomas. Another study on comparison of SVZ+ and SVZ- GBM patients identified role of hemopexin and other proteins. In this symposium we will present our results from these studies that demonstrate the utilization of proteomics to provide mechanistic insight of glioma pathogenesis and identification of potential biomarkers.