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5,8 We examined the expressions of EP4 and EP2 mRNA (PTGER4 and PTGER2, respectively). We observed elevated PTGER4 expression in normal breast tissue samples compared with malignant breast samples (Fig. 2F, check details solid box). Of the tumor samples, basal and HER2-enriched tumors (dashed box) showed higher PTGER4 expression than the luminal subtype tumors (dotted box). These data support our previous findings that EP4 could be a therapeutic target in more aggressive breast cancer subtypes. PTGER2 is more highly expressed in normal breast tissue compared with malignant breast tissue. There seems to be no relationship between breast cancer subtype and PTGER2 expression (Fig. 2G). Comparing the same region of multiple panels allowed us to qualitatively identify the differences in gene expression among specific subtypes of cancer. To this point, our data suggested that TNBC is distinct from the other subtypes with respect to COX-2 pathway expression. These trends between breast cancer subtypes and PGE2 pathway member gene expression patterns warranted a deeper analysis into TCGA data. The Illumina HiSeq dataset was downloaded using the UCSC Cancer Genome Browser and analyzed. TNBC samples (n = 123) were compared with all other primary tumor samples (n = 964) across the five PGE2 pathway genes. Expression of PTGS2 Oxygenase (COX-2) and ABCC4 (MRP4) mRNA was significantly higher (P NU7441 molecular weight were significantly decreased in the TNBC samples compared with other primary tumor samples. PTGER4 (EP4) mRNA expression was similar in all groups. Taken together, this pattern of gene expression should lead to more PGE2 synthesis and export to the tumor microenvironment and less import and degradation in the setting of TNBC. These results illustrate fundamental differences between TNBC and other types of breast cancer. Given these patterns, we would expect that PGE2 levels in TNBC tumors would be elevated due to the increased production and export and decreased metabolism of PGE2. Figure 3 Expression of PGE2 pathway genes in TNBC samples favors production and extracellular accumulation of PGE2. Primary breast cancer samples were classified into Other and TNBC based on ER, PR, and HER2 receptor protein expression status. The distribution ... There were 810 patients with complete records available to estimate OS; 93 patients (11.5%) were confirmed dead at the time of data entry. OS was defined as the time from initial diagnosis to death from any cause, censored at the date of last contact. RFS was estimated using 792 cases. RFS was defined as the time from initial diagnosis to disease recurrence.