Circulating miR-148b and miR-133a as biomarkers for breast cancer detection.

// Jie Shen 1 , Qiang Hu 2,5 , Michael Schrauder 6 , Li Yan 2 , Dan Wang 2 , Leonardo Medico 3 , Yuqing Guo 3 , Song Yao 3 , Qianqian Zhu 2 , Biao Liu 2 , Maochun Qin 2 , Matthias W. Beckmann 6 , Peter A. Fasching 6 , Reiner Strick 6 , Candace S. Johnson 4 , Christine B. Ambrosone 3 , Hua Zhao 1 , Song Liu 2 1 Department of Epidemiology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA 2 Department of Biostatistics & Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY, USA 3 Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA 4 Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY, USA 5 Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, P.R.China 6 Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany Correspondence: Hua Zhao, email: // Song Liu, email: // Keywords : circulating microRNAs, breast cancer, biomarkers, detection Received : March 10, 2014 Accepted : May 26, 2014 Published : May 26, 2014 Abstract Circulating microRNAs have drawn a great deal of attention as promising novel biomarkers for breast cancer. However, to date, the results are mixed. Here, we performed a three-stage microRNA analysis using plasma samples from breast cancer patients and healthy controls, with efforts taken to address several pitfalls in detection techniques and study design observed in previous studies. In the discovery phase with 122 Caucasian study subjects, we identified 43 microRNAs differentially expressed between breast cancer cases and healthy controls. When those microRNAs were compared with published data from other studies, we identified three microRNAs, including miR-148b, miR-133a and miR-409-3p, whose plasma levels were significantly higher in breast cancer cases than healthy controls and were also significant in previous independent studies. In the validation phase with 50 breast cancer cases and 50 healthy controls, we validated the associations with breast cancer detection for miR-148b and miR-133a (P = 1.5×10 -6 and 1.3×10 -10 , respectively). In the in-vitro study phase, we found that both miR-148b and miR-133a were secreted from breast cancer cell lines, showing their secretory potential and possible tumor origin. Thus, our data suggest that both miR-148b and miR-133a have potential use as biomarkers for breast cancer detection.