RNA expression signatures of ONB from Classe et al., 2018 based on markers traditionally associated with sinonasal undifferentiated carcinoma (A), small cell neuroendocrine carcinoma (B), and olfactory neuroblastoma (C), divided by control OE, low grade ONB, high grade ONB, and IDH2 mutant ONB. A) Expression of keratins is not significantly increased in IDH2 mutant ONB versus IDH2 wild type tumors. B) Small cell neuroendocrine carcinoma (SNEC) marker genes are not highly expressed ONB from Classe et al. dataset. C) Expression of canonical neuroendocrine markers is negatively associated with ONB grade, and is not significantly different between high grade IDH2 and high grade IDH2 mutant ONB.
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.
