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Deregulated MicroRNA as Potential Biomarker of Early Stage Breast Cancer Open Access

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AbstractMicroRNAs (miRNAs) are a highly abundant class of endogenous non-coding RNAs (18-25 nucleotides in length), which contributes to cancer initiation and progression by silencing the expression of their target genes, causing either mRNA molecule degradation or translational inhibition. Intraductal epithelial proliferations of the breast are histologically and clinically classified into normal, ductal epithelial hyperplasia (DEH), atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS). To better understand the progression of ductal breast cancer development and distinguish between the normal, ADH and DCIS conditions, we attempt to identify deregulated miRNAs in the process using eight patients' Formalin-Fixed, Paraffin-Embedded (FFPE) breast tissues. Following tissue microdissection, we obtained 8 normal, 4 ADH, 6 DCIS and 7 IDC (invasive ductal carcinoma) samples, which were used for miRNA expression profiling analysis. We found a significant number of deregulated miRNAs comparing ADH with normal, which indicates miRNA expression changes as an early event during tumor initiation. In particular, we observed miR-21, miR-200b/c, miR-141, and miR-183 were consistently up-regulated in ADH, DCIS and IDC compared to normal; while, miR-557 was uniquely down-regulated in DCIS. Interestingly, we did not find a step-wise broad-wide miRNA alterations among discrete stages along the tumor progression, which are in accordance with previous reports of mRNA profiling of different stages of breast cancer. This study has demonstrated the feasibility of using FFPE tissues for miRNA expression analysis, and identified a number of miRNAs that may be used as biomarkers for early stage breast cancer detection and management.

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