Abstract
Expression of olfactory receptors (ORs) has been reported in many human tissues outside the nasal epithelium. ORs have been validated as biomarkers in prostate cancer. In breast cancer, however, the expression and role of OR genes remain understudied. We examined the significance of OR transcript abundance in a large invasive breast carcinoma population and identified two OR genes, OR2W3 and OR2B6 to be potentially correlated to breast cancer progression. 960 breast invasive tumors and 56 human breast cancer cell lines were assessed for OR gene expression and 21 OR genes were highly abundant among 198 cases. Our transcriptome analysis discovered three significantly abundant OR genes among three sub-populations of invasive breast carcinoma patients. OR2W3 was correlated with invasion genes and basal-like subtype whereas OR2B6 was correlated with proliferation genes and luminal A subtype. Analyzing the OR gene upregulation among breast cancer cell lines showed that OR2B6 and OR2W3 were abundant similar to invasive breast tumors. Our study suggests that specific OR genes may be correlated with breast cancer characteristics, making ORs potential new diagnostic, and/or treatment markers. This study suggests future directions for the exploration of a role for ORs in the mechanisms of breast cancer proliferation and progression.
Highlights
Expression of olfactory receptors (ORs) has been reported in many human tissues outside the nasal epithelium
Using The Cancer Genome Atlas (TCGA) breast invasive carcinoma study and the cancer cell line encyclopedia (CCLE), we analyzed the abundance of OR gene expression for each and the presence of shared OR genes among invasive breast carcinoma cases and human breast cancer cell lines
Clustered heatmap of human breast cancer cell lines based on their upregulation of the over-expressed OR genes demonstrated three distinct cell line groups, each with exclusive upregulation of one OR gene. (B) Quantitative comparison of the upregulation levels reveals that OR2B6 is significantly upregulated in cell line group I, OR5AU1 is significantly upregulated in cell line group II and OR2W3 is significantly expressed in cell line group III (*p < 0.05, One-way ANOVA). (C) 90% of breast cancer cell lines in group III were triple-negative breast cancer (TNBC) cell lines. (D) The majority of breast cancer cell lines possess high-level amplification in the OR genes with significant abundance
Summary
Expression of olfactory receptors (ORs) has been reported in many human tissues outside the nasal epithelium. We examined the significance of OR transcript abundance in a large invasive breast carcinoma population and identified two OR genes, OR2W3 and OR2B6 to be potentially correlated to breast cancer progression. 960 breast invasive tumors and 56 human breast cancer cell lines were assessed for OR gene expression and 21 OR genes were highly abundant among 198 cases. Using The Cancer Genome Atlas (TCGA) breast invasive carcinoma study and the cancer cell line encyclopedia (CCLE), we analyzed the abundance of OR gene expression for each and the presence of shared OR genes among invasive breast carcinoma cases and human breast cancer cell lines Availability of both RNAseq data and DNA copy number alterations across a large patient population, along with clinical survival data, makes TCGA an ideal data source for our comparative investigation. The simultaneous abundance of breast cancer-related genes and OR genes opens the possibility of ORs as key role-players in breast cancer
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