Identifying a GBM Transcriptomic Signature in Differential Sensitivity to an Inhibitor of Protein Stability
Targeted therapeutics are an imperative approach in finding treatments for Glioblastoma Multiforme (GBM) patients. GBM is a heterogeneous brain tumor known for its aggressiveness. With the ability to attain transcriptomic data to personally identify individuals, the motivation here is a specific treatment for a specific person. Four cell lines were analyzed across 10 combinations of drug dosage and time, with three replicates creating 120 samples. Differential gene expression (DGE) analysis was performed on these samples to derive the most significant changes in transcriptomic expression that were conflicting between sensitive and non-sensitive cell lines. Gene set variation analysis (GSVA) was also conducted for biological insight. Multiple gene sets were found to be differentially enriched, matching the sensitivity of the cell cultures, notable sets include: E2F Transcription Factor Targets, MYC Targets, and Epithelial Mesenchymal Transition. Through the initial exploration of genes within these gene sets, CCNE1 and CCNE2 are examples of an ideal candidate in signifying how change in expression level can give insight to differential sensitivity between the experimental groups. With further in vitro validation, these transcriptomic anomalies may contribute to a more efficient patient screening process that leads to higher success rates.
