Abstract:
Ectopically expressed olfactory receptors (ORs) have been linked with multiple clinicallyrelevant physiological processes. Previously used tissue-level expression estimation largely
shadowed the potential role of ORs due to their overall low expression levels. Even after the
introduction of the single-cell transcriptomics, a comprehensive delineation of expression
dynamics of ORs in tumors remained unexplored. Our targeted investigation into single
malignant cells revealed a complex landscape of combinatorial OR expression events. We
observed differentiation-dependent decline in expressed OR counts per cell as well as their
expression intensities in malignant cells. Further, we constructed expression signatures based
on a large spectrum of ORs and tracked their enrichment in bulk expression profiles of tumor
samples from The Cancer Genome Atlas (TCGA). TCGA tumor samples stratified based on
OR-centric signatures exhibited divergent survival probabilities. In summary, our comprehensive analysis positions ORs at the cross-road of tumor cell differentiation status and
cancer prognosis.
