Assinatura transcricional especifica de genes da transição epitélio- mesenquimal mdicam alterações fenotípícas em células tumorais circulantes durante o desenvolvimento do câncer de mama

Abstract

Background: Breast cancer is a global health problem. Tumor cell phenotype is essential for the progression of breast cancer (BC) and the epithelial-mesenchymal transition (EMT) allows tumor cells to acquire characteristics that will allow them to invade and migrate to secondary sites. The aim of this study was to evaluate the transcriptional profile of epithelial and mesenchymal markers, seeking to evaluate the mechanisms driving the circulating tumor cells (CTCs) during cancer initiation and progression and to propose possible markers that aid in the evaluation of treatment effectiveness. Methods: Three groups were considered: BC patients with and without chemotherapy (CT), and patients with benign breast disease (BBD). Breast tumor tissue was collected to analyze the presence of tumor cells. Peripheral blood was collected to analyze the presence of circulating tumor cells (CTCs). RNA was extracted and real-time PCR was performed to analyze the transcriptional levels of EMT markers in blood and tissue in patients with BBD, BC without CT and BC with CT. Results: Data from medical records of 87 patients were analyzed; 25 women were diagnosed with BBD and 62 with BC. The CK6a, CK18, vimentin, MMP9 and CD44 genes had elevated levels of transcriptional genes in the peripheral blood in the BC group without CT compared to the other groups. CD44 had elevated levels of transcriptional genes were higher in the in situ tumor (estadio 0), had a decrease in the intermediate stages and returned to increase in later stages. The same result was found in tumor differentiation grade. In view of these results we postulate our a new hypothetical model of development of breast cancer. Conclusion: The process of altering the phenotype of CTCs is relevant and occurs early in cancer development. Moreover, EMT markers may be useful in the clinical routine to monitor the effectiveness of CT.