Our objective is to identify correlates of neural signaling in relation to glioma histopathology and patient outcomes.

We used a combination of bulk RNA sequencing and a DNA 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 a Cox-model fit. All analyses were conducted using R.

180 paired patient samples were analyzed for RNA-seq and DPG. t-SNE of DGE highlights two distinct functional clusters with no correlation to WHO classification status (Chi-squared p > 0.1) The median survival for the big cluster was observed at 934 days, while no median survival was reached even after 7,250 days of follow-up in the small cluster (p = 0.048). This contrast remains consistent when examining subsets of gliomas with unmethylated MGMT promoter (p = 0.022) and glioblastomas (p = 0.046), but not others such as IDH mutation status and low-grade gliomas (p > 0.1). 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 (67% and 33%). DPG of low-grade gliomas highlighted 3 somatic signaling mutations (EPHB2, GPC3, and AXL) that are more prevalent in the big cluster.