Proteogenomic characterization and biomarker discovery in glioblastoma

Division Of Basic Sciences - Nci

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Abstract

Methods: 82 pts diagnosed with pathology proven glioblastoma (2005-2013) were enrolled on IRB approved protocol 04-C-0020 and treated with concurrent chemoirradiation with blood and urine biospecimens obtained prior to and following completion of radiation therapy. Serum was then screened using the aptamer-based SOMAscan proteomic assay technology, for changes in expression of 7000 protein analytes. Employing each patient as their own control, biomarker expression was initially analysed using Graphpad and IPA to identify preliminary proteomic signatures representative of biological mechanisms involved in ionizing radiation, and hallmarks of cancer including angiogenesis, stemness and metabolism. These were then correlated using clinical data (pt age, gender), tumor related factors (extent of resection), radiation therapy volumes (GTV, PTV), outcomes (PFS, OS). Further work will be aimed at: 1) Replicating and extending possible differential proteomic biomarker expression pre vs post radiation therapy. 2) Connecting large scale proteomic data to upstream pathways and genomic analysis to identify proteogenomic clusters defining radiation resistance and response and prognosis. 3) Validation with large scale public data sets (eg TCGA/TCIA and others). 4) Exploring differential biomarker expression prior to radiation therapy as compared to glioma subtypes described in the literature. 5) Exploring differential biomarker expression post radiation therapy in relationship to recurrence and survival and existing data on proteins associated with predictive and/or prognostic value. 6) Aggregating proteomic and proteogenomic results with AI driven progression criteria in glioma (currently subject of imaging analysis with Artificial Intelligence Resource (AIR)) and validation with large scale public data sets.