Proteogenomic characterization and integrative analysis of glioblastoma multiforme.

ABSTRACT

Glioblastoma multiforme (GBM), the most aggressive and lethal primary brain tumor, is characterized by very low life expectancy. Understanding the genomic and proteogenomic characteristics of GBM is essential for devising better therapeutic approaches.Here, we performed proteomic profiling of 8 GBM and paired normal brain tissues. In parallel, comprehensive integrative genomic analysis of GBM was performed in silico using mRNA microarray and sequencing data. Two whole transcript expression profiling cohorts were used - a set of 3 normal brain tissues and 22 glioma tissue samples and a cohort of 5 normal brain tissues and 49 glioma tissue samples. A validation cohort included 529 GBM patients from The Cancer Genome Atlas datasets. We identified 36 molecules commonly changed at the level of the gene and protein, including up-regulated TGFBI and NES and down-regulated SNCA and HSPA12A. Single amino acid variant analysis identified 200 proteins with high mutation rates in GBM samples. We further identified 14 differentially expressed genes with high-level protein modification, among which NES and TNC showed differential expression at the protein level. Moreover, higher expression of NES and TNC mRNAs correlated with shorter overall survival, suggesting that these genes constitute potential biomarkers for GBM.