Y-box binding protein YBX1 and its correlated genes as biomarkers for poor outcomes in patients with breast cancer

// Tomohiro Shibata 1 , Eriko Tokunaga 2 , Satoshi Hattori 3 , Kosuke Watari 1 , Yuichi Murakami 1, 4 , Nami Yamashita 5 , Eiji Oki 5 , Junji Itou 6 , Masakazu Toi 6 , Yoshihiko Maehara 7 , Michihiko Kuwano 4 and Mayumi Ono 1 1 Department of Pharmaceutical Oncology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan 2 National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan 3 Department of Integrated Medicine, Biomedical Statistics, Osaka University Graduate School of Medicine, Osaka, Japan 4 Cancer Translational Research Center, St. Mary's Institute of Health Sciences, Kurume, Japan 5 Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan 6 Department of Breast Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan 7 Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, Fukuoka, Japan Correspondence to: Mayumi Ono, email: mono@phar.kyushu-u.ac.jp Keywords: YBX1; ER; breast cancer; predictive biomarker; antiestrogen resistance Received: November 08, 2018      Accepted: December 05, 2018      Published: December 14, 2018 ABSTRACT The enhanced expression of the Y-box binding protein YBX1 is consistently correlated with poor outcomes or reduced survival of breast cancer patients. However, the mechanism underlying the association between increased YBX1 expression and poor outcomes has yet to be revealed. We searched a database for the top 500 genes that are positively or negatively correlated with YBX1 and with ESR1 in breast cancer patients. We further examined the association between YBX1-correlated genes and breast cancer outcomes in patients at Kyushu University Hospital. More than 60% of genes that are positively correlated with YBX1 are also negatively correlated with ESR1. The enhanced expression levels of the top 20 positively correlated genes mostly predict negative outcomes, while the enhanced expression levels of the top 20 negatively correlated genes mostly predict positive outcomes. Furthermore, in breast cancer patients at Kyushu University Hospital, the expression levels of YBX1 and YBX1-positively correlated genes were significantly higher and the expression levels of genes negatively correlated with YBX1 were significantly lower in patients who relapsed after their primary surgery than in those who did not relapse. The expression of YBX1 together with the expression of its positively or negatively correlated genes may help to predict outcomes as well as resistance to endocrine therapies in breast cancer patients. Determining the expression of YBX1 and its closely correlated genes will contribute to the development of precision therapeutics for breast cancer.