Shibata Tomohiro, Tokunaga Eriko, Hattori Satoshi, Watari Kosuke, Murakami Yuichi, Yamashita Nami, Oki Eiji, Itou Junji, Toi Masakazu, Maehara Yoshihiko, Kuwano Michihiko, Ono Mayumi
Department of Pharmaceutical Oncology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.
Oncotarget. 2018 Dec 14;9(98):37216-37228. doi: 10.18632/oncotarget.26469.
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.
Y盒结合蛋白YBX1的表达增强与乳腺癌患者的不良预后或生存期缩短一直相关。然而，YBX1表达增加与不良预后之间关联的潜在机制尚未明确。我们在一个数据库中搜索了与乳腺癌患者中YBX1及雌激素受体1（ESR1）呈正相关或负相关的前500个基因。我们进一步研究了九州大学医院患者中与YBX1相关基因和乳腺癌预后之间的关联。与YBX1呈正相关的基因中，超过60%也与ESR1呈负相关。前20个正相关基因的表达水平增强大多预示着不良预后，而前20个负相关基因的表达水平增强大多预示着良好预后。此外，在九州大学医院的乳腺癌患者中，初次手术后复发的患者中YBX1及其正相关基因的表达水平显著高于未复发患者，而与YBX1呈负相关基因的表达水平则显著低于未复发患者。YBX1的表达及其正相关或负相关基因的表达可能有助于预测乳腺癌患者的预后以及对内分泌治疗的耐药性。确定YBX1及其密切相关基因的表达将有助于开发乳腺癌的精准治疗方法。
