Pluripotency genes expression in glioma-initiating stem cells and clinical outcome.

Abstract

e12509 Background: Accurate prognostic markers are required for patients with glioblastoma multiforme. Recent studies have demonstrated a relationship between the expression of stem cell-associated genes and relapses in glioblastoma, suggesting a key role of tumor stem cells in this process. The aim of this study was to identified tumor stem cell-associated markers in glioblastoma by monitoring pluripotency and stemness-related genes expression and to evaluate their potential prognostic value. Methods: By using TaqMan Low Density Array (TLDA), a highly specific and sensitive gene expression technology, the pluripotency genes expression profiles were analysed in glioblastoma-derived neurospheres from 11 patients undergoing surgery. After enrichment of the tumor-initiating stem cell population, gene expression profiling was performed and compared to human embryonic stem cells (hES). Following hierarchical clustering, differentially expressed genes were assessed in neurospheres and further confirmed in an independent cohort of 30 patients with glioblastoma. Results: Hierarchical clustering analyses revealed 8 differentially expressed genes in neurospheres and primary tumors, among which COL1A1 and IFITM1 with the highest expression levels. Considering COL1A1 and IFITM1 expression and clinical data (overall survival), Kaplan-Meier survival analysis clearly demonstrated that COL1A1 and IFITM1 overexpression were associated with a longer survival (10.5 months versus 17.5 months, p<10-3). Conclusions: COL1A1 and IFITM1 pluripotency genes could be used for stratifying patients with glioblastoma into subgroups for risk of recurrence at diagnosis, as well as for prognostic and therapeutic evolution.