{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T04:20:43Z","timestamp":1783570843405,"version":"3.55.0"},"reference-count":37,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,4,28]],"date-time":"2021-04-28T00:00:00Z","timestamp":1619568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Medical Research Council (NMRC) of Singapore","award":["NMRC\/CBRG\/0087\/2015"],"award-info":[{"award-number":["NMRC\/CBRG\/0087\/2015"]}]},{"name":"National Medical Research Council of Singapore","award":["NMRC\/CBRG\/0087\/2015"],"award-info":[{"award-number":["NMRC\/CBRG\/0087\/2015"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/cancers13092130","type":"journal-article","created":{"date-parts":[[2021,4,28]],"date-time":"2021-04-28T10:41:58Z","timestamp":1619606518000},"page":"2130","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Development of a microRNA Panel for Classification of Abnormal Mammograms for Breast Cancer"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3177-2762","authenticated-orcid":false,"given":"Ruiyang","family":"Zou","sequence":"first","affiliation":[{"name":"Department of Research and Development, MiRXES Lab, Singapore 138623, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sau Yeen","family":"Loke","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Research, Humphrey Oei Institute of Cancer Research, National Cancer Centre Singapore, Singapore 169610, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronique Kiak-Mien","family":"Tan","sequence":"additional","affiliation":[{"name":"SingHealth Duke-NUS Oncology Academic Clinical Programme, Duke-NUS Medical School, Singapore 169857, Singapore"},{"name":"National Cancer Centre Singapore, Division of Surgery and Surgical Oncology, Singapore 169610, Singapore"},{"name":"Department of Breast Surgery, Singapore General Hospital, Singapore 169608, Singapore"},{"name":"SingHealth Duke-NUS Breast Centre, Singapore 169610, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7561-7492","authenticated-orcid":false,"given":"Swee Tian","family":"Quek","sequence":"additional","affiliation":[{"name":"Departments of Diagnostic Imaging, National University Hospital and Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pooja","family":"Jagmohan","sequence":"additional","affiliation":[{"name":"Departments of Diagnostic Imaging, National University Hospital and Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0890-7822","authenticated-orcid":false,"given":"Yew Chung","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Research and Development, MiRXES Lab, Singapore 138623, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Preetha","family":"Madhukumar","sequence":"additional","affiliation":[{"name":"SingHealth Duke-NUS Oncology Academic Clinical Programme, Duke-NUS Medical School, Singapore 169857, Singapore"},{"name":"National Cancer Centre Singapore, Division of Surgery and Surgical Oncology, Singapore 169610, Singapore"},{"name":"Department of Breast Surgery, Singapore General Hospital, Singapore 169608, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benita Kiat-Tee","family":"Tan","sequence":"additional","affiliation":[{"name":"SingHealth Duke-NUS Oncology Academic Clinical Programme, Duke-NUS Medical School, Singapore 169857, Singapore"},{"name":"National Cancer Centre Singapore, Division of Surgery and Surgical Oncology, Singapore 169610, Singapore"},{"name":"Department of Breast Surgery, Singapore General Hospital, Singapore 169608, Singapore"},{"name":"SingHealth Duke-NUS Breast Centre, Singapore 169610, Singapore"},{"name":"Department of General Surgery, Sengkang General Hospital, Singapore 544886, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei Sean","family":"Yong","sequence":"additional","affiliation":[{"name":"SingHealth Duke-NUS Oncology Academic Clinical Programme, Duke-NUS Medical School, Singapore 169857, Singapore"},{"name":"National Cancer Centre Singapore, Division of Surgery and Surgical Oncology, Singapore 169610, Singapore"},{"name":"Department of Breast Surgery, Singapore General Hospital, Singapore 169608, Singapore"},{"name":"SingHealth Duke-NUS Breast Centre, Singapore 169610, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8758-0455","authenticated-orcid":false,"given":"Yirong","family":"Sim","sequence":"additional","affiliation":[{"name":"SingHealth Duke-NUS Oncology Academic Clinical Programme, Duke-NUS Medical School, Singapore 169857, Singapore"},{"name":"National Cancer Centre Singapore, Division of Surgery and Surgical Oncology, Singapore 169610, Singapore"},{"name":"SingHealth Duke-NUS Breast Centre, Singapore 169610, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sue Zann","family":"Lim","sequence":"additional","affiliation":[{"name":"SingHealth Duke-NUS Oncology Academic Clinical Programme, Duke-NUS Medical School, Singapore 169857, Singapore"},{"name":"National Cancer Centre Singapore, Division of Surgery and Surgical Oncology, Singapore 169610, Singapore"},{"name":"Department of Breast Surgery, Singapore General Hospital, Singapore 169608, Singapore"},{"name":"SingHealth Duke-NUS Breast Centre, Singapore 169610, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunice","family":"Png","sequence":"additional","affiliation":[{"name":"SingHealth Polyclinics, Singapore 150167, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu Yun Sherylyn","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Tan Tock Seng Hospital, Singapore 308433, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mun Yew Patrick","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Tan Tock Seng Hospital, Singapore 308433, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teng Swan Juliana","family":"Ho","sequence":"additional","affiliation":[{"name":"SingHealth Duke-NUS Oncology Academic Clinical Programme, Duke-NUS Medical School, Singapore 169857, Singapore"},{"name":"National Cancer Centre Singapore, Division of Oncologic Imaging, Singapore 169610, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boon Kheng James","family":"Khoo","sequence":"additional","affiliation":[{"name":"SingHealth Duke-NUS Oncology Academic Clinical Programme, Duke-NUS Medical School, Singapore 169857, Singapore"},{"name":"National Cancer Centre Singapore, Division of Oncologic Imaging, Singapore 169610, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su Lin Jill","family":"Wong","sequence":"additional","affiliation":[{"name":"National Cancer Centre Singapore, Division of Oncologic Imaging, Singapore 169610, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Choon Hua","family":"Thng","sequence":"additional","affiliation":[{"name":"SingHealth Duke-NUS Oncology Academic Clinical Programme, Duke-NUS Medical School, Singapore 169857, Singapore"},{"name":"National Cancer Centre Singapore, Division of Oncologic Imaging, Singapore 169610, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bee Kiang","family":"Chong","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Radiology, Tan Tock Seng Hospital, Singapore 308433, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yik Ying","family":"Teo","sequence":"additional","affiliation":[{"name":"Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore 117549, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng-Phon","family":"Too","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikael","family":"Hartman","sequence":"additional","affiliation":[{"name":"Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore 117549, Singapore"},{"name":"Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore 119228, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ngiap Chuan","family":"Tan","sequence":"additional","affiliation":[{"name":"SingHealth Polyclinics, Singapore 150167, Singapore"},{"name":"SingHealth Duke-NUS Family Medicine Academic Clinical Programme, Duke-NUS Medical School, Singapore 169857, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ern Yu","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Tan Tock Seng Hospital, Singapore 308433, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo Chin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Hematology-Oncology, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore 119228, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Research and Development, MiRXES Lab, Singapore 138623, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9719-9332","authenticated-orcid":false,"given":"Ann Siew Gek","family":"Lee","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Research, Humphrey Oei Institute of Cancer Research, National Cancer Centre Singapore, Singapore 169610, Singapore"},{"name":"SingHealth Duke-NUS Oncology Academic Clinical Programme, Duke-NUS Medical School, Singapore 169857, Singapore"},{"name":"Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117593, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Sung, H., Ferlay, J., Siegel, R.L., Laversanne, M., Soerjomataram, I., Jemal, A., and Bray, F. 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