microRNA Expression in Ethnic Specific Early Stage Breast Cancer: an Integration and Comparative Analysis

Abstract

Breast cancer (BC) has a higher incidence in young Lebanese woman as compared to the West. We assessed the microRNA (miRNA) microarray profile of tissues derived from Lebanese patients with early BC and performed mRNA-miRNA integration analysis. 173 miRNAs were significantly dysregulated in 45 BC versus 17 normal adjacent breast tissues, including 74 with a fold change more than two of which 17 were never reported before in cancer. Integration analysis of mRNA-miRNA microarray data revealed a potential role of 51 dysregulated miRNA regulating 719 tumor suppressive or oncogenic mRNA associated with increased proliferation and decreased migration and invasion. We then performed a comparative miRNA microarray profile analysis of BC tissue between these 45 Lebanese and 197 matched American BC patients. Notably, Lebanese BC patients had 21 exclusively dysregulated miRNA (e.g. miR-31, 362-3p, and 663) and 4 miRNA with different expression manner compared to American patients (e.g. miR-1288-star and 324-3p). Some of these differences could reflect variation in patient age at diagnosis or ethnic variation affecting miRNA epigenetic regulation or sequence of miRNA precursors. Our data provide a basis for genetic/epigenetic investigations to explore the role of miRNA in early stage BC in young women, including ethnic specific differences.

miRNA expression in advanced Algerian breast cancer tissues

“…miR-183 upregulation coincides with the results of a study by Chen et al where miR-183, in addition to miR-21 and miR-200c were find to be significantly upregulated in the FFPE breast cancer tissues [25]. This was also noted in a study on Lebanese FFPE breast cancer tissues [20,31]. miR-182 upregulation was noted in more than one study where its fold change of expression is usually more than 4 folds higher in cancerous breast tissue than in paracancerous tissue [32].…”

“…In addition, it was difficult to obtain some of the clinical characteristics of some patients due to cross country and institutional barriers. miR-21, miR-183, miR-182, miR-425-5p and miR-200c were found to be upregulated in tumor versus normal adjacent breast tissues, similar to the Lebanese patients and patients in other studies reported in the literature [20,25]. This study is the first to report the patterns of miRNA dysregulation in the Algerian population, one of North African populations that are known to possess great gene pool heterogeneity from Eurasia, Sub Saharan Africa and North Africa [49].…”

“…The downregulation of miR-125b and miR-100 in the present study, to the contrary of study on samples of Lebanese patients, did not reach significance. This similarity is expected as both Algerian and Lebanese patients have a similar ethnic profile and lie within the Middle East and North Africa region [20]. A limitation of the study is the small sample size that did not offer us adequate power to study relationships between the clinical characteristics and miRNA deregulation.…”

“…The deregulation of miRNAs such as miR-21, miR-425-5p, miR-183, miR-182, miR-200c, miR-125b and miR-100 has been studied extensively in the literature, as well as in breast cancer tissues of neighboring Arab populations as in Lebanon [20]. The latter study is the only array available for breast cancer tissues in the MENA for the Arab population and it shows that miR-183, miR-miR-182, miR-200c, miR-425-5p and miR-21 were significantly upregulated while miR-125b and 100 were significantly downregulated in tumor versus normal adjacent tissues.…”

MiR-663, a MicroRNA Linked with Inflammation and Cancer That Is under the Influence of Resveratrol

“…Breast cancer has a higher incidence in young Lebanese women as compared with American woman. A comparative profiling study showed that, in Lebanese breast cancer patients, 21 miRNAs, including miR-663 , were specifically deregulated, possibly as a result of differential methylation of their promoter [ 46 ]. Another study showed that miR-663 is up-regulated in multidrug-resistant MDA-MB-231-derived ADM cell line, and that increased miR-663 expression was associated with the downregulation of Heparin sulfate proteoglycan 2 (HSPG2) and chemoresistance [ 47 ].…”