Signatures of circulating microRNAs in diagnosis and prognosis of women with breast cancer

Abstract

Breast cancer is the most common tumor type in women, and the main cause of death in these patients is tumor progression and the development of metastases. The identification of tumor markers that can predict tumor behavior is of particular interest to scientific community. Currently, the molecular characterization of several types of tumors, including breast cancer, has traditionally been performed on samples obtained from tumor biopsy or surgical resection. However, in recent years, liquid biopsy has been gaining ground as a promising detection tool for tumors, with the benefit of being less invasive. Among biological fluids, blood has a good potential to carry circulating markers, as it travels throughout the body reflecting the sum of physiological processes. MicroRNAs (miRNAs) are small molecules of non-coding mRNA that play a key role in gene regulation. Recent studies have shown that miRNAs are directly involved in the initiation and progression of various tumor types, including breast cancer. Several studies point to the presence of tumor markers in serum or plasma, however, there are still few studies that evaluate miRNAs as possible tumor markers in the blood. Thus, the purpose of this study is performing a validation approach to identify the signature of four circulating miRNAs being, 2 oncogenes (miR-210 and miR-155) and 2 tumor suppressors (miR-200 and miR-152) with differentiated expression in women with breast cancer. Blood samples will be collected from 30 women diagnosed with breast cancer and 15 healthy women (control). The samples will be processed to obtain the plasma, and RNA extraction and its quantification will be performed. For the analysis of miRNAs expression, the cDNAs will be synthesized and then real-time PCR. In addition, in a retrospective study, paraffin blocks will be selected belonging to the Service of Pathology of the Base Hospital of São José do Rio Preto, and have already been included in previous studies by our research group and with a follow-up of 10 years. In these blocks, analyzes of miRNAs expression and quantification of the target proteins will be performed, verifying the prognostic value of this signature. Therefore, this study aims to contribute to the validation of miRNAs signatures that can be used as a potential non-invasive tool for diagnosis and prognosis in breast cancer. (AU)