Characterizing Glioblastoma Multiforme By Linking Molecular Profiles to Macro Phenotypes

Glioblastoma multiforme (GBM) is an aggressive brain cancer without effectivetreatment options, leaving patient survival rates extremely low. HDAC1 knockdown was found to initiate an invasive phenotype in vivo, particularly within the BT145 human glioma stem cell (hGSC) line. Analysis through RNA sequencing (RNA-seq) gene expression and regulatory networks found both CEBPβ, a known transcription factor (TF) involved in cellular invasion, and the STAT3 pathway, a notorious genetic component of GBM, were differentially expressed in BT145 hGSCs after HDAC1 knockdown. Furthermore, overlap of genes regulated by CEBPβ and STAT3 indicate the CEBPβ/STAT3 pathway may be involved in the observed BT145- specific invasive phenotype. The SYstems Genetics Network AnaLysis (SYGNAL) pipeline was applied to construct sex-specific gene regulatory networks from The Cancer Genome Atlas (TCGA) GBM patient expression data. Unique bicluster eigengenes were discovered separately for all, female, and male patients. Through the application of these bicluster eigengenes to a GBM cohort with multiparametric magnetic resonance imaging (mpMRI) localized biopsies, sex-specific associations between bicluster expression, mpMRI readout, and hallmarks of cancer were determined. Distinctive cancer functions were revealed transcriptionally through bicluster expression, and connected to a unique mpMRI feature. Specifically, SPGRC mpMRI indicated a strong signal for both immune hallmarks (evading immune detection and tumor-promoting inflammation). At the same time, MD mpMRI displayed a tendency toward sustained angiogenesis, possibly signaling the formation of new blood vessels. Uncovering each mpMRI feature’s underlying biological processes enables improved GBM diagnosis and treatment utilizing an individualized, non-invasive approach.