Eye absent 2(EYA2)蛋白是一种酪氨酸磷酸酶，在多种癌中高表达。我们应用全转录组测序分析和免疫组化技术研究发现EYA2在铂类耐药上皮性卵巢癌组织中显著高表达，且与患者的预后负相关，过表达EYA2能促进上皮性卵巢癌细胞增殖、迁移侵袭和抑制细胞凋亡，通过质谱等鉴定EYA2能够与拓扑异构酶1（TOP1）相结合，并能去磷酸化TOP1及促进其胞浆转位，并发现TOP1与凋亡因子APAF1结合。本课题拟分别从细胞、组织等多种角度研究EYA2基因表达对肿瘤化疗耐药影响及临床上的相关性，重点阐明EYA2对TOP1去磷酸化的位点以及促进TOP1胞浆转位机制，鉴定出TOP1直接与凋亡体APAF1相结合的区段，明确TOP1的非核内非经典功能，探讨靶向EYA2在体内外对上皮性卵巢癌耐药的克服作用，为深入理解上皮性卵巢癌耐药机理提供新的实验依据，为上皮性卵巢癌的精准诊治提供新的策略。

Eye absent 2(EYA2) is a kind of tyrosine phosphatase, which is overexpressed in many different tumor types. Occupying Using the whole transcriptome sequencing and immunohistochemical analysis, we had found that EYA2 was significantly expressed in the epithelial ovarian cancer which was resistant to platinum. And the expression of EYA2 was negatively associated with the prognosis of the patients. Overexpression of EYA2 could promote proliferation, migration, and invasion and inhibit apoptosis of epithelial ovarian cancer cells. Further, we applied Mass Spectrometry and other technologies to explore the molecular mechanism of EYA2 promoting tumor growth. And we found that EYA2 could bind to TOP1, following by dephosphorylating TOP1, then TOP1 was translocated to cytoplasm from nucleus, and TOP1 bound to APAF1. We will further study the correlation between EYA2 expression and chemoresistance or clinicopathologic features of epithelial ovarian cancer from various aspects such as tissue and cell studies. We will clearly illustrate the dephosphorylation site of TOP1 by EYA2 phosphatase and the mechanism of TOP1 nucleo-cytoplasmic translocation. Furthermore, we will identify the exact region of TOP1 and EYA2 binding, confirming the non-canonical function of TOP1 out of nucleus. Finally, we will explore whether targeting EYA2 can reverse the chemoresistance of epithelial ovarian cancer in vitro and in vivo. In summary, our research will improve our understanding of chemoresistance and provide new strategies for precision treatment of epithelial ovarian cancer.