Advances in cancer therapy and diagnosis have led to an increase in the survival rate of women with breast cancer (BC). However, for metastatic BC, the 5-year relative survival rate remains about 30%. Previously, we identified miRNAs potentially regulated by estrogen, progesterone, or androgen receptors (ER, PR, and AR), the change in the level of which was associated with the presence of lymph nodes metastases (LNM) in patients with BC (miR-193b, -190a, -190b, -21). The most common method for cancer diagnosis is immunohistochemical analysis. Therefore, the search for protein markers is an urgent task. In this study, we identified putative target genes for the above miRNAs that are expressed predominantly in breast tissue according to The Human Protein Atlas (https://www.proteinatlas.org). We analyzed the expression of selected genes in BC samples.
We quantified the level of mRNAs by real-time PCR in MCF-7 cells treated for 6, 24, 48 hours with 100 nM of estradiol (E2), progesterone (P4), or testosterone (T), and in BC samples (n=117). BC tissue samples and samples of normal adjacent tissue from female patients who had not received preoperative pharmacotherapy were collected at Novosibirsk Municipal Clinical Hospital #1. The statistical analysis was carried out using the Mann–Whitney U test.
OXTR, TRPS1, STC2, and AKR1C2 were selected for analysis. OXTR mRNA level increased in cells after incubation with all hormones. The most significant increase was in cells treated with E2 for 48 h (increased by 2.4-fold). TRPS1 mRNA level increased 1.6-fold in cells treated with E2 for 48 h. STC2 mRNA level increased 1.4-fold in cells treated with E2 or T for 6 h. AKR1C2 mRNA level decreased by 1.4-fold in cells treated with T for 24 and 48 h. Expression of E2-sensitive OXTR, STC2, TRPS1 increased in ER- and/or PR-positive tumors as compared to ER-and-PR-negative tumors. OXTR and TRPS1 (higher level of mRNA in tumors of patients with LNM) were found to be associated with presence of LNM in luminal tumors not expressing HER2.
Our study indicates the association between the expression of OXTR, STC2, TRPS1 and ER expression in BC. We discovered that increased OXTR and TRPS1 mRNA level is a potential marker of LNM in ER- and/or PR-positive tumors with HER2 IHC score 0.
Legal entity responsible for the study
Russian Science Foundation, grant number: 19-15-00319.
All authors have declared no conflicts of interest.