Study of microRNAs-21/221 as potential breast cancer biomarkers in Egyptian women

Date published

2016-01-29

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Elsevier

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Article

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0378-1119

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Tarek Mohamed Kamal Motawi, Nermin Abdel Hamid Sadik, Olfat Gamil Shaker, Maha Rafik El Masry, Fady Mohareb, Study of microRNAs-21/221 as potential breast cancer biomarkers in Egyptian women, Gene, Volume 590, Issue 2, 30 September 2016, Pages 210-219

Abstract

microRNAs (miRNAs) play an important role in cancer prognosis. They are small molecules, approximately 17–25 nucleotides in length, and their high stability in human serum supports their use as novel diagnostic biomarkers of cancer and other pathological conditions. In this study, we analyzed the expression patterns of miR-21 and miR-221 in the serum from a total of 100 Egyptian female subjects with breast cancer, fibroadenoma, and healthy control subjects. Using microarray-based expression profiling followed by real-time polymerase chain reaction validation, we compared the levels of the two circulating miRNAs in the serum of patients with breast cancer (n = 50), fibroadenoma (n = 25), and healthy controls (n = 25). The miRNA SNORD68 was chosen as the housekeeping endogenous control. We found that the serum levels of miR-21 and miR-221 were significantly overexpressed in breast cancer patients compared to normal controls and fibroadenoma patients. Receiver Operating Characteristic (ROC) curve analysis revealed that miR-21 has greater potential in discriminating between breast cancer patients and the control group, while miR-221 has greater potential in discriminating between breast cancer and fibroadenoma patients. Classification models using k-Nearest Neighbor (kNN), Naïve Bayes (NB), and Random Forests (RF) were developed using expression levels of both miR-21 and miR-221. Best classification performance was achieved by NB Classification models, reaching 91% of correct classification. Furthermore, relative miR-221 expression was associated with histological tumor grades. Therefore, it may be concluded that both miR-21 and miR-221 can be used to differentiate between breast cancer patients and healthy controls, but that the diagnostic accuracy of serum miR-21 is superior to miR-221 for breast cancer prediction. miR-221 has more diagnostic power in discriminating between breast cancer and fibroadenoma patients. The overexpression of miR-221 has been associated with the breast cancer grade. We also demonstrated that the combined expression of miR-21 and miR-221can be successfully applied as breast cancer biomarkers.

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Keywords

MiRNA, miR-21, miR-221, Breast cancer, Fibroadenoma

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Published by Elsevier. This is the Author Accepted Manuscript issued with: Creative Commons Attribution Non-Commercial No Derivatives License (CC:BY:NC:ND 3.0). The final published version (version of record) is available online at http://dx.doi.org/10.1016/j.gene.2016.01.042. Please refer to any applicable publisher terms of use. Attribution-Non-Commercial-No Derivatives 3.0 Unported (CC BY-NC-ND 3.0). You are free to: Share — copy and redistribute the material in any medium or format. The licensor cannot revoke these freedoms as long as you follow the license terms. Under the following terms: Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use. Information: Non-Commercial — You may not use the material for commercial purposes. No Derivatives — If you remix, transform, or build upon the material, you may not distribute the modified material. No additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.

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