Analysis of single-cell transcriptomes links enrichment of olfactory receptors with cancer cell differentiation status and prognosis

Ectopically expressed olfactory receptors (ORs) have been linked with multiple clinically-relevant 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. Through analyses of olfactory receptors in single-cell RNA sequencing dataset from different cancers, Kalra, Mittal et al. find that the number and expression levels of olfactory receptors vary by differentiation status. The study provides insights into an under-appreciated role for olfactory receptors in cancer pathogenesis.