40P - Patient-based models to study infiltration heterogeneity in gliomas

Background

Despite advances in understanding the molecular basis of high-grade gliomas, glioblastoma (GBM) still represents a challenge in terms of therapy. Beside tumor heterogeneity, one of the features hindering the efficacy of treatments is the highly infiltrative nature of glioma cells that, by hydrodynamic cellular volume changes,invade brain parenchyma along narrow extracellular routes. GSC have been reported as the putative population responsible for GBM resistance to treatments and recurrences. Aim of the study was to use a Precision Medicine (PM) approach by taking advantage of patient-derived in vitro models to give insight into the heterogeneity of the molecular pathways underlying the infiltration process.

Methods

GSC were obtained from 15 patients undergoing surgery for a newly diagnosed GBM. GSC were analysed in terms of: 1. invasive attitude by using an ad hoc in vitro migration assay; 2. transcriptional profile, by next generation sequencing. Bioinformatic was employed to define a genetic signature, and to validate its prognostic role in 500 GBM tissues included in TCGA/GTEX datasets.

Results

The in vitro study revealed that each cell line was characterized by a distinct migratory behavior, confirming that GSC recapitulated the intrinsic heterogeneity of the original tumors. Moreover, migrating and non-migrating GSC showed a distinctive transcriptional profile and, correlating differentially expressed genes with GBM included in TCGA/GTEX datasets, we identified a GSC-based signature predictive of GBM patient’s prognosis.

Conclusions

This study outlines the role of patient-based stem cells models as a tool to deepen insights on GBM features and to discover new biomarkers useful in identifying adjuvant therapies targeting the infiltration process.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

University of Udine.

Funding

University of Udine.

Disclosure

All authors have declared no conflicts of interest.