蒽环类药物是乳腺癌化疗一线药物，其耐药是困扰临床应用的重要问题，筛选其敏感性标志物具有显著临床意义。课题组长期专注水通道蛋白（AQP），尤其是AQP1在乳腺癌中的作用。我们前期明确了AQP1在乳腺癌中的胞浆表达，首次报道AQP1胞浆表达与乳腺癌患者预后显著负相关。深入研究又发现（1）AQP1胞浆高表达患者可从CEF方案中获益，不能从CMF方案中获益，提示AQP1胞浆表达与蒽环类药物疗效密切相关；（2）AQP1与β-catenin在乳腺癌细胞胞浆中共定位并相互作用；（3）乳腺癌患者中AQP1与β-catenin二者胞浆表达正相关；接受CEF方案患者中二者均胞浆高表达患者预后最好。据此课题组提出AQP1胞浆表达可作为乳腺癌蒽环类药物疗效的标志物，AQP1胞浆高表达可通过β-catenin信号通路增加蒽环类药物疗效的原创性假说并进行验证，是前期国家自然科学基金青年项目和面上项目的延续和深入研究。

Anthracycline-based therapies are part of the standard of care in first line treatment of metastatic breast cancer and their clinical use is widespread. Chemoresistance of anthracycline is the important problem to be overcome in clinic at present and screening anthracycline sensitive biomarkers is urgently needed. Our group has been focused on research of AQP (water channels) family, especially the function of AQP1 in breast cancer development. Our previous reports firstly discovered the cytoplasmic expression of AQP1 in breast cancer and disclaimed that high expression of AQP1 was negatively associated with prognosis of breast cancer patients for the first time. Furthermore, our resent work found that (1) patients with high expression of AQP1 have better prognosis in CEF regimens than those who were treated with CMF regimens. It indicated that AQP1 was associated with the anthracycline-based therapies. (2) AQP1 could have co-localization and interaction with β-catenin in cytoplasm. (3) Expression of AQP1 was positively associated with β-catenin in breast cancer patients and only patients with both high expression of AQP1 and β-catenin had best outcome among patients with CEF regimens. Therefore, our group demonstrated the new hypothesis that expression of AQP1 in cytoplasm may be biomarker of anthracycline-based therapies and it probably enhance the therapeutic effect of anthracycline through β-catenin signaling, we will confirm the hypothesis by this project. The present project is the continuous research work of our previous NSFC projects.