MicroRNA Expression as a Prognostic Indicator for Breast Cancer Development. Summary of the Doctoral Thesis

Abstract

Breast cancer is the most wide spread tumor and the most frequent cause of death among women worldwide. Breast cancer is clinically, morphologically and genetically diverse disease therefore the outcome of the disease and treatment is dependent on the molecular heterogeneity of the disease. Breast cancer can be subdivided in several different molecular subtypes and this classification algorithm in the clinical practice is used to evaluate the pace of the disease and possible outcome. This algorithm has been used for more than 10 years already, thought this algorithm is not enough informative to predict the pace and the outcome of the disease. Hence in clinical practice new – more informative biomarkers are required. One of such potential biomarker could be microRNAs – non-coding small RNA molecules that have the ability to regulate gene expression post-transcriptionally, and they are involved in the cell differentiation, growth, and apoptosis. In tumors, microRNA expression is changed, and there is a correlation between the changed expression and clinical features of the disease MicroRNAs can act either as tumor inducers or tumor suppressors, and either are up-regulated or down-regulated. The TN breast cancer patients harboring the BRCA1 gene mutation at the time of the diagnosis are younger, have smaller tumor size, and have significantly better recurrence-free and disease-specific survival than TN breast cancer patients with no mutations in the BRCA1 gene. This study attempt to associate altered expression levels of some microRNAs (miR-10b, miR-21, miR-29a miR-31, and miR-214) in TNH and TNS cancer tissues to disease specific survival. In this study different gene expression profiles between TNH and TNS breast cancer tissues were evaluated as well. Four microRNAs (miR-10b, miR-21, miR-31, and miR-214) showed higher expression level in sporadic tissues than in hereditary ones; however only miR-214 was significantly higher. The triple-negative breast cancer patients with high level of miR-214 showed worse disease-specific survival than those with low level. In addition, 20 differently expressed gene were found between TNH and TNS breast cancer tissues. Moreover, three of those genes: C12ORF23, C1ORF19, and AMMECR1L are regulated by the miR-21 and miR-214.