The detection of circulating biomarkers by liquid biopsy is of great importance for early diagnosis and prognosis and, thus, can contribute to decreasing the mortality rate of women with breast cancer (BC). The high mortality of BC is related to the occurrence of metastasis, a process that is associated with angiogenesis. The angiogenic process, in turn, is related to the stimulation of pro-angiogenic factors (among them: Insulin-like Growth Factor 1 Receptor - IGF-1R; Hypoxia-Inducible Factors 1α - HIF-1α and Vascular Endothelial Growth Factor - VEGF) and inhibition of anti-angiogenic factors (such as Von Hippel-Lindau protein - VHL). In addition, the regulation of this neovascularization by epigenetic mechanisms involving microRNAs (miRs) is being investigated and, in BC, oncomiR-210 and the tumor suppressor microRNA-152 stand out in this process.
Plasma samples and tumor fragments were collected from women with BC, with benign breast conditions (BBC) and from healthy women (control). For analysis of microRNA expression, the complementary DNA synthesis was performed followed by real-time Polymerase Chain Reaction (qPCR). For the analysis of the expression of the target proteins, immunohistochemistry was then carried out. Values of p < 0.05 were considered significant.
In the plasma samples of women with BC, an increase in the expression of miR-210 and miR-152 was observed. As expected, our results also showed increased oncomiR-210 expression and decreased miR-152 in the fragments of BC. As potential prognostic markers, miR-210 was able to differentiate fragments of BC from good prognosis to poor prognosis. In addition, miR-152 was able to differentiate prognosis in plasma. Finally, it was found that the HIF-1α, IGF-1R and VEGF proteins showed increased expression in BC, whereas the VHL protein presented a decrease.
The increased expression of these microRNAs in liquid biopsy of women with BC is promising in the diagnosis and prognosis of this neoplasm, and makes them potential biomarkers for patients with BC. We also confirmed the oncogenic action of miR-210 and tumor suppression of miR-152 on breast cancer fragments validated by the expression of their target proteins.
LIMC - Laboratório de Investigação Molecular do Câncer da Faculdade de Medicina de São José do Rio Preto (FAMERP).
Fundação de Amparo a Pesquisa do Estado de São Paulo - FAPESP (Proc. nº 17/11807-3).
All authors have declared no conflicts of interest.