Y-box binding protein YBX1 and its correlated genes as biomarkers for poor outcomes in patients with breast cancer
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Tomohiro Shibata1, Eriko Tokunaga2, Satoshi Hattori3, Kosuke Watari1, Yuichi Murakami1,4, Nami Yamashita5, Eiji Oki5, Junji Itou6, Masakazu Toi6, Yoshihiko Maehara7, Michihiko Kuwano4 and Mayumi Ono1
1Department of Pharmaceutical Oncology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan
2National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan
3Department of Integrated Medicine, Biomedical Statistics, Osaka University Graduate School of Medicine, Osaka, Japan
4Cancer Translational Research Center, St. Mary's Institute of Health Sciences, Kurume, Japan
5Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
6Department of Breast Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
7Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, Fukuoka, Japan
Mayumi Ono, email: [email protected]
Keywords: YBX1; ER; breast cancer; predictive biomarker; antiestrogen resistance
Received: November 08, 2018 Accepted: December 05, 2018 Published: December 14, 2018
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.
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