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. 2018 Jun 26:9:683.
doi: 10.3389/fphar.2018.00683. eCollection 2018.

Review and Meta-Analyses of TAAR1 Expression in the Immune System and Cancers

Lisa M Fleischer  1 , Rachana D Somaiya  1 , Gregory M Miller  1   2   3
Affiliations

Review and Meta-Analyses of TAAR1 Expression in the Immune System and Cancers

Lisa M Fleischer et al. Front Pharmacol. .

Abstract

Since its discovery in 2001, the major focus of TAAR1 research has been on its role in monoaminergic regulation, drug-induced reward and psychiatric conditions. More recently, TAAR1 expression and functionality in immune system regulation and immune cell activation has become a topic of emerging interest. Here, we review the immunologically-relevant TAAR1 literature and incorporate open-source expression and cancer survival data meta-analyses. We provide strong evidence for TAAR1 expression in the immune system and cancers revealed through NCBI GEO datamining and discuss its regulation in a spectrum of immune cell types as well as in numerous cancers. We discuss connections and logical directions for further study of TAAR1 in immunological function, and its potential role as a mediator or modulator of immune dysregulation, immunological effects of psychostimulant drugs of abuse, and cancer progression.

Keywords: B-cell; PBMC; T-cell; astrocyte; granulocyte; lymphocyte; microglia; platelet.

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Figures

Figure 1
Figure 1
Differential RNAseq expression data for TAAR1 in human cancers. A TAAR1 mRNA transcript query in BioXpress (Wan et al., 2015) revealed that TAAR1 is upregulated in esophageal, lung, and stomach cancers, and downregulated in sarcoma, cervical, renal, kidney, liver, pancreas, pituitary, prostate, urinary, and uterine cancers. This differential expression is statistically significant in esophageal (*p = 0.023) and prostate (**p = 0.000043) cancers.
Figure 2
Figure 2
Meta-analysis of the prognostic value of TAAR1 expression in overall cancer survival. Forest plot of hazard ratios for survival in 80 human cancer studies representing 15 cancer types were obtained from open-source repositories (PROGgene n = 68, Prognoscan n = 12). Hazard ratios were determined for TAAR1 expression bifurcated into high and low expression and all HR values were log-transformed to normalize values around zero to enable the calculation of subgroup averages and then back transformed to produce the average HR value for each cancer type.
Figure 3
Figure 3
RNAseq analysis of TAAR1 expression in human TCGA cancer cohorts. RNAseq expression datasets representing cohorts from 36 cancer types were downloaded from The Cancer Genome Atlas (TCGA) using the R package RTCGA.rnaseq and values for the TAAR1 gene transcript were extracted, log2 transformed, and plotted with ggplot2. The minimal non-zero value for RNA expression levels was set to 1 to facilitate log2 transformation.
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