1345 Correlates of Neural Signaling Elucidate Survival Benefit in Gliomas

INTRODUCTION: Recent literature has highlighted neural signaling markers (SM) as drivers for synaptogenesis, invasion, and proliferation in gliomas. Further work on elucidating key mutations can provide not only improved prognostication but also potential treatment targets. METHODS: We used a combination of bulk RNA sequencing (RNA-seq) and a DNA sequencing gene panel (DPG) by Tempus next-generation sequencing. Differential gene expression (DGE) was performed using DESeq2 after subsetting genes for neural SM. Dimensionality reduction was applied through t-SNE projections. Variant calls were analyzed using EnsemblVEP and maftools. Survival analysis was determined through log-rank tests. All analyses were conducted using R. RESULTS: 176 and 184 patient samples were analyzed for RNA-seq and DPG, respectively. t-SNE of DGE highlights two distinct functional clusters with no correlation to WHO classification status (Chi-squared p = 0.15). The median survival for the big cluster was observed at 957 days, while no median survival was reached even after 4,420 days of follow-up in the small cluster (p = 0.01). Genes upregulated in the small cluster had equal representation of synaptic and paracrine SM (45% and 55%), while the big cluster had a greater representation of paracrine SM (69% and 31%). This contrast remains consistent when examining subsets of gliomas with unmethylated MGMT promoter (p = 0.02) and high-grade gliomas (p = 0.055), but not others such as IDH status and low-grade gliomas (p > 0.1). DPG of low-grade gliomas highlighted 3 somatic signaling mutations (FGFR1, PTPRD, and SLIT2) that are more prevalent in the big cluster. CONCLUSIONS: Functional classification based on neural signaling markers can elucidate a novel set of biomarkers that may impact survival in glioma patients. Further studies are required to validate such findings and develop therapeutic targets.