Seifu, Daniel(Associate Professor of Biochemistry Department of Biochemistry, AAU)Mulugeta, Yonas (Dr.)2019-02-062023-11-292019-02-062023-11-292018-09http://etd.aau.edu.et/handle/123456789/16259reast cancer is the second most common cause of death from cancer in women. There is now increased prevalence of breast cancer among African women. In Ethiopia it is the leading cancer type constituting 33% of all cancer cases in women. It is a heterogeneous type of disease which comprises of many biologically different and pathologically distinct features that lead to different treatment responses. Tests and procedures for diagnosis and prognosis of breast cancer are still limited to invasive procedures and imaging techniques. Based on their differential expression in disease and with their exceptional stability in biological fluids, microRNAs are noticeable candidates to be used as non-invasive diagnostic and prognostic biomarker. The association of change in expression level of microRNAs with clinicopathological parameters may demonstrate their potential in sorting the heterogeneous disease to specific subgroups for effective treatment options. The purpose of this study was to investigate the differential expression of specific circulatory microRNAs in breast cancer patients and study their association with clinicopathological parameters with samples from healthy volunteers serving as control. Changes in the level of microRNA after completing chemotherapy was also assessed and checked for association with serum CA 15-3 values to see the prognostic potential of specific microRNAs. XIV The levels of specific circulatory microRNAs in patient and control samples were analyzed using qRT-PCR. Serum CA 15-3 values from patient samples collected after completion of chemotherapy were measured using solid phase enzyme linked immunosorbent assay. In this study miRNA 21-5p was significantly over expressed in the serum of breast cancer patients when compared with controls (P<0.05). Receiver operating characteristic curve analysis shows its potential in differentiating breast cancer patients from controls with AUC value of 0.6 (P<0.05). A significant decrease in serum miR-326 was observed after chemotherapy (P<0.05) as compared to serum samples collected before chemotherapy. No correlations was found between serum CA 15-3 values and levels of circulatory microRNAs. Mean serum CA 15-3 value of patients with stage IV breast cancer was found to be high when compared with patients with other stages (P<0.001). Well-designed studies are required to elucidate the clinical validity of deregulated microRNAs in breast cancer to be used as diagnostic and prognostic biomarkers. Since deregulated miRNAs in the circulation are shared by several cancer types and subtypes, further studies are necessary to identify a well characterized cluster of miRNAs with discriminative ability.en-USBreast cancer,heterogeneousThesis