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.

异位表达的嗅觉受体 (OR) 与多种临床相关的生理过程有关。以前使用的组织水平表达估计在很大程度上掩盖了 ORs 的潜在作用，因为它们的整体表达水平较低。即使在引入单细胞转录组学之后，对肿瘤中 OR 表达动态的全面描述仍未得到探索。我们对单个恶性细胞的有针对性的研究揭示了组合 OR 表达事件的复杂情况。我们观察到每个细胞表达的 OR 计数及其在恶性细胞中的表达强度的分化依赖性下降。更远，我们基于大范围的 OR 构建了表达特征，并跟踪了它们在来自癌症基因组图谱 (TCGA) 的肿瘤样本的大量表达谱中的富集情况。基于 OR 中心特征分层的 TCGA 肿瘤样本表现出不同的生存概率。总之，我们的综合分析将 OR 定位在肿瘤细胞分化状态和癌症预后的十字路口。