Invadomics Identification and Validation of Potential Genetic Targets Associated with Glioma Invasion
Anderson, EM1,2; Demuth, T2; Reavie, LB2; Hoelzinger, DB2; Rennert, JL2; Nakada, S2; Nakada, M2; and Berens, ME2
1Harrington Department of Bioengineering, Arizona State University, Tempe, AZ; 2Translational Genomics Research Institute, Phoenix, AZ
Glioblastoma multiforme (GBM), the most advanced form of a large subset of brain tumors collectively known as glioma, is the most aggressive and invasive type of brain tumor. Patients usually experience a median survival range of 9 to 12 months. GBMs are extremely difficult to manage because of the tumor cells tendency to migrate and pervade into adjacent tissues. Surgical resection, chemotherapy and radiation therapy of GBMs generally only slows disease progression because invasive cells are poorly targeted by these treatments and they proceed to migrate through brain tissues and reform a new tumor mass. It is hypothesized that the invasive phenotype of these tumor cells may be attributable to unique gene expression relative to non-invasive tumor cells. Stationary core and invasive rim tumor cells were collected separately by laser capture microdissection (LCM) from 19 biopsy samples. Whole genome expression analysis of RNA collected from each sample was carried out and t-test was performed to identify genes differentially expressed between the two populations. A priori knowledge was used to select candidate genes for technical validation by quantitative real-time PCR (QRT-PCR). We will report results from QRT-PCR validation and clinical validation on a comprehensive expression data set of human gliomas. Further validation of protein expression in clinical tumor samples will be performed by immunohistochemistry on a tissue microarray. In vitro assays focused on glioma cell line migration, invasion and cytotoxicity will then be used to study the effect of inhibiting protein synthesis of the target gene by short interfering RNA (siRNA).