MicroRNA expression analyses in a panel of early breast cancer tissues derived from Lebanese patients -

Abstract

Breast cancer is the most common type of cancer among Lebanese women. Lebanon has an elevated level of age standardized breast cancer incidence and mortality. Besides, Lebanon has a higher prevalence of patients younger than 40 years old as compared to developed countries. These young patients usually present with worse prognosis in spite of chemo- and hormonal therapy, and they mostly lack BRCA gene mutations. Moreover, patients below 40 years have no available screening tests for early breast cancer detection. Hence, our study focuses on investigating molecular mechanisms that underlie breast cancer development and that could be later used as a biomarker for early detection and prognosis. Our molecule of interest is microRNA (miRNA), a class of noncoding RNA, which regulates 60percent of gene expression posttranscriptionally by binding to target mRNA leading to its degradation or translational repression. miRNA has been shown to be dysregulated in breast cancer and to play a role at the different stages of mammary tumorigenesis. We first conducted a pilot study to find the expression of miR-10b, 21, 155, 148b, 221 in 57 tumor and 20 normal adjacent formalin fixed paraffin embedded (FFPE) tissues taken from Lebanese breast cancer patients of various clinical and histopathological presentations. These chosen miRNA were significantly dysregulated in breast cancer based on literature; however, miR-148b was significantly upregulated and miR-221 showed no change in expression in our samples as opposed to what is reported. Thus, this difference in miRNA expression could be attributed to ethnicity of the patients. For this purpose, we performed a global miRNA microarray profiling on 45 tumor and 17 normal adjacent FFPE mammary tissues collected from Lebanese breast cancer patients with early stage invasive ductal carcinoma histotype and positive estrogen and progesterone receptor. Results have shown 74 significantly dysregulated miRNA in tumor versus normal adjacent tissues which are mostly newly discovered miRNA or have ne