Circulating microRNAs as Specific Biomarkers for Breast Cancer Detection |
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Authors: | Enders K. O. Ng Rufina Li Vivian Y. Shin Hong Chuan Jin Candy P. H. Leung Edmond S. K. Ma Roberta Pang Daniel Chua Kent-Man Chu W. L. Law Simon Y. K. Law Ronnie T. P. Poon Ava Kwong |
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Affiliation: | 1Department of Surgery, The University of Hong Kong, Hong Kong, China;2Department of Clinical Oncology, The University of Hong Kong, Hong Kong, China;3Department of Molecular Pathology, Hong Kong Sanatorium and Hospital, Hong Kong, China;4Biomedical Research Center, Sir Runrun Shaw Hospital, Medical School of Zhejiang University, Hangzhou, China;The University of Kansas Medical Center, United States of America |
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Abstract: | BackgroundWe previously showed microRNAs (miRNAs) in plasma are potential biomarkers for colorectal cancer detection. Here, we aimed to develop specific blood-based miRNA assay for breast cancer detection.Methodology/Principal FindingsTaqMan-based miRNA profiling was performed in tumor, adjacent non-tumor, corresponding plasma from breast cancer patients, and plasma from matched healthy controls. All putative markers identified were verified in a training set of breast cancer patients. Selected markers were validated in a case-control cohort of 170 breast cancer patients, 100 controls, and 95 other types of cancers and then blindly validated in an independent set of 70 breast cancer patients and 50 healthy controls. Profiling results showed 8 miRNAs were concordantly up-regulated and 1 miRNA was concordantly down-regulated in both plasma and tumor tissue of breast cancer patients. Of the 8 up-regulated miRNAs, only 3 were significantly elevated (p<0.0001) before surgery and reduced after surgery in the training set. Results from the validation cohort showed that a combination of miR-145 and miR-451 was the best biomarker (p<0.0001) in discriminating breast cancer from healthy controls and all other types of cancers. In the blind validation, these plasma markers yielded Receiver Operating Characteristic (ROC) curve area of 0.931. The positive predictive value was 88% and the negative predictive value was 92%. Altered levels of these miRNAs in plasma have been detected not only in advanced stages but also early stages of tumors. The positive predictive value for ductal carcinoma in situ (DCIS) cases was 96%.ConclusionsThese results suggested that these circulating miRNAs could be a potential specific biomarker for breast cancer screening. |
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