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Development of a microRNA Panel for Classification of Abnormal Mammograms for Breast Cancer

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Department of Research and Development, MiRXES Lab, Singapore 138623, Singapore
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Cellular and Molecular Research, Humphrey Oei Institute of Cancer Research, National Cancer Centre Singapore, Singapore 169610, Singapore
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SingHealth Duke-NUS Oncology Academic Clinical Programme, Duke-NUS Medical School, Singapore 169857, Singapore
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National Cancer Centre Singapore, Division of Surgery and Surgical Oncology, Singapore 169610, Singapore
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Department of Breast Surgery, Singapore General Hospital, Singapore 169608, Singapore
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SingHealth Duke-NUS Breast Centre, Singapore 169610, Singapore
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Departments of Diagnostic Imaging, National University Hospital and Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
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Department of General Surgery, Sengkang General Hospital, Singapore 544886, Singapore
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SingHealth Polyclinics, Singapore 150167, Singapore
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Department of General Surgery, Tan Tock Seng Hospital, Singapore 308433, Singapore
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National Cancer Centre Singapore, Division of Oncologic Imaging, Singapore 169610, Singapore
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Department of Diagnostic Radiology, Tan Tock Seng Hospital, Singapore 308433, Singapore
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Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore 117549, Singapore
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Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore
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Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore 119228, Singapore
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SingHealth Duke-NUS Family Medicine Academic Clinical Programme, Duke-NUS Medical School, Singapore 169857, Singapore
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Department of Hematology-Oncology, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore 119228, Singapore
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Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117593, Singapore
*
Authors to whom correspondence should be addressed.
Cancers 2021, 13(9), 2130; https://doi.org/10.3390/cancers13092130
Received: 24 March 2021 / Revised: 22 April 2021 / Accepted: 26 April 2021 / Published: 28 April 2021
(This article belongs to the Section Cancer Biomarkers)
Breast cancer screening by mammography suffers from high rates of false positivity, resulting in unnecessary investigative imaging and biopsies. There is an unmet need for biomarkers that can distinguish between malignant and benign breast lesions. We performed miRNA profiling on 638 patients with abnormal mammograms and 100 healthy controls. A six-miRNA panel was identified and validated in an independent cohort that had an AUC of 0.881 when differentiating between cases versus those with benign lesions or healthy individuals with normal mammograms. In addition, biomarker panel scores increased with tumor size, stage and number of lymph nodes involved. This study demonstrates that circulating miRNAs can potentially be used in conjunction with mammography to differentiate between patients with malignant and benign breast lesions.
Mammography is extensively used for breast cancer screening but has high false-positive rates. Here, prospectively collected blood samples were used to identify circulating microRNA (miRNA) biomarkers to discriminate between malignant and benign breast lesions among women with abnormal mammograms. The Discovery cohort comprised 72 patients with breast cancer and 197 patients with benign breast lesions, while the Validation cohort had 73 and 196 cancer and benign cases, respectively. Absolute expression levels of 324 miRNAs were determined using RT-qPCR. miRNA biomarker panels were identified by: (1) determining differential expression between malignant and benign breast lesions, (2) focusing on top differentially expressed miRNAs, and (3) building panels from an unbiased search among all expressed miRNAs. Two-fold cross-validation incorporating a feature selection algorithm and logistic regression was performed. A six-miRNA biomarker panel identified by the third strategy, had an area under the curve (AUC) of 0.785 and 0.774 in the Discovery and Validation cohorts, respectively, and an AUC of 0.881 when differentiating between cases versus those with benign lesions or healthy individuals with normal mammograms. Biomarker panel scores increased with tumor size, stage and number of lymph nodes involved. Our work demonstrates that circulating miRNA signatures can potentially be used with mammography to differentiate between patients with malignant and benign breast lesions. View Full-Text
Keywords: breast cancer; abnormal mammograms; circulating microRNAs; biomarkers; qRT-PCR breast cancer; abnormal mammograms; circulating microRNAs; biomarkers; qRT-PCR
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Figure 1

MDPI and ACS Style

Zou, R.; Loke, S.Y.; Tan, V.K.-M.; Quek, S.T.; Jagmohan, P.; Tang, Y.C.; Madhukumar, P.; Tan, B.K.-T.; Yong, W.S.; Sim, Y.; Lim, S.Z.; Png, E.; Lee, S.Y.S.; Chan, M.Y.P.; Ho, T.S.J.; Khoo, B.K.J.; Wong, S.L.J.; Thng, C.H.; Chong, B.K.; Teo, Y.Y.; Too, H.-P.; Hartman, M.; Tan, N.C.; Tan, E.Y.; Lee, S.C.; Zhou, L.; Lee, A.S.G. Development of a microRNA Panel for Classification of Abnormal Mammograms for Breast Cancer. Cancers 2021, 13, 2130. https://doi.org/10.3390/cancers13092130

AMA Style

Zou R, Loke SY, Tan VK-M, Quek ST, Jagmohan P, Tang YC, Madhukumar P, Tan BK-T, Yong WS, Sim Y, Lim SZ, Png E, Lee SYS, Chan MYP, Ho TSJ, Khoo BKJ, Wong SLJ, Thng CH, Chong BK, Teo YY, Too H-P, Hartman M, Tan NC, Tan EY, Lee SC, Zhou L, Lee ASG. Development of a microRNA Panel for Classification of Abnormal Mammograms for Breast Cancer. Cancers. 2021; 13(9):2130. https://doi.org/10.3390/cancers13092130

Chicago/Turabian Style

Zou, Ruiyang, Sau Y. Loke, Veronique K.-M. Tan, Swee T. Quek, Pooja Jagmohan, Yew C. Tang, Preetha Madhukumar, Benita K.-T. Tan, Wei S. Yong, Yirong Sim, Sue Z. Lim, Eunice Png, Shu Y.S. Lee, Mun Y.P. Chan, Teng S.J. Ho, Boon K.J. Khoo, Su L.J. Wong, Choon H. Thng, Bee K. Chong, Yik Y. Teo, Heng-Phon Too, Mikael Hartman, Ngiap C. Tan, Ern Y. Tan, Soo C. Lee, Lihan Zhou, and Ann S.G. Lee. 2021. "Development of a microRNA Panel for Classification of Abnormal Mammograms for Breast Cancer" Cancers 13, no. 9: 2130. https://doi.org/10.3390/cancers13092130

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