Tumor demographics separated by Hyams grade, Dulguerov T stage, and gene expression groups (low versus high) used for survival analysis in Figure 5 and Figure S4. Average Ki-67 mRNA expression obtained from bulk RNA-Seq outputs. Average Ki-67 index obtained from histology data reported by Classe et al., 2018. +/- in the last two columns is standard error of the mean (SEM).
ARTICLE ABSTRACT
Olfactory neuroblastoma is a rare tumor arising from the olfactory cleft region of the nasal cavity. Due to the low incidence of this tumor, as well as an absence of established cell lines and murine models, understanding the mechanisms driving olfactory neuroblastoma pathobiology has been challenging. Here, we sought to apply advances from research on the human olfactory epithelial neurogenic niche, along with new biocomputational approaches, to better understand the cellular and molecular factors in low- and high-grade olfactory neuroblastoma and how specific transcriptomic markers may predict prognosis. We analyzed a total of 19 olfactory neuroblastoma samples with available bulk RNA-Sequencing and survival data, along with 10 samples from normal olfactory epithelium. A bulk RNA-Sequencing deconvolution model identified a significant increase in globose basal cell (GBC) and CD8 T cell identities in high grade tumors (GBC from approximately 0% to 8%, CD8 T cell from 0.7% to 2.2%), and significant decreases in mature neuronal, Bowman’s gland, and olfactory ensheathing programs, in high grade tumors (mature neuronal from 3.7% to approximately 0%, Bowman’s gland from 18.6% to 10.5%, olfactory ensheathing from 3.4% to 1.1%). Trajectory analysis identified potential regulatory pathways in proliferative olfactory neuroblastoma cells, including PRC2, which was validated by immunofluorescence staining. Survival analysis guided by gene expression in bulk RNA-Sequencing data identified favorable prognostic markers such as SOX9, S100B, and PLP1 expression.
