Evolution of Oncogenic Signatures Within Glioblastoma Along a Spatiotemporal Axis
ISEF · 2022 Biomedical and Health Sciences Fourth Award
Overview
Glioblastoma is a malignant tumor of the central nervous system distinguished by its intra-tumoral heterogeneity and inevitable recurrence. A longitudinal axis of genomic evolution has been identified between two spatially defined identities, tumor edge and core. This study sought to characterize this transition as a potential therapeutic target. Publicly available RNA-seq data was used to identify significant differentially expressed genes. These DEGs (n=105) were then further analyzed at both the individual gene level and at the whole genome level. Transcription factor enrichment analysis revealed the oncogenic transcription factor FOXM1 as a statistically significant mediator of downregulated target genes. Protein-protein interaction network analysis of DEGs revealed the oncogenic protein kinase MELK as over-represented within the core. The protein complex of MELK and FOXM1 has been characterized to transcriptionally regulate the enzymatic catalytic subunit EZH2, which in turn promotes radio-resistance. Clinically, the co-expression of EZH2 and MELK is induced in recurrent tumors. Small molecules and drugs that reverse this spatiotemporal gene expression signature were identified. Collectively, this systematic comparison of tumor core/edge and the identification of DEGs as critical instigators of therapeutic resistance provides a coherent portrait of the prognostically-significant shift in molecular phenotypes associated with the spatiotemporal axis. This intra-patient heterogeneity highlights the importance of eradication of the tumor edge to prevent the lethal GBM recurrence. Additionally, these data link this lethal axis to the edge-to-core transition and indicate MELK-FOXM1-driven EZH2 signaling as a therapeutic target in postsurgical GBM tumors.
Awards (1)
- Fourth Award of $500 $500
Competition history
- ISEF 2022
Resources
Related projects
JSHS · 2023
Evolution of Oncogenic Signatures within Glioblastoma Along a Spatiotemporal Axis
ISEF · 2021
Intratumoral Heterogeneity in Gene Expression within Single Glioblastoma Tumors
ISEF · 2021
Comparative Analysis of Genetic Mutations and Overall Survival in Patients with Glioblastoma Multiforme: A Retrospective Cohort Study
ISEF · 2024
The Effect of Somatic Mutations in Glioblastoma Multiforme on Patient Survival
ISEF · 2021
Differential Expression Analysis and Transcriptomic Characterization of Glioma Progression
ISEF · 2025
Molecular Arsonists: Degrading Oncogenic Transcription Factors to Reverse Tumor Cell Immortality
ISEF · 2017
Characterization of Patient-Derived Glioblastoma Cell Lines
JSHS · 2020
GLIA-Deep: Glioblastoma Image Analysis using Deep Learning Convolutional Neural Networks to Accurately Classify Gene Methylation and Predict Drug Effectiveness Viraj Mehta
Closest projects by meaning, across every fair and year in the corpus.
Browse more like this
Source: Regeneron International Science and Engineering Fair