人附睾蛋白4（HE4）是目前敏感性及特异性最高的卵巢癌标志物，相关研究主要集中在其作为标志物对卵巢癌的诊断及预后评估等方面，机制研究极少且较粗浅。我们发现：1.膜联蛋白A2（ANXA2）可能为HE4的受体；2.HE4 与S100A10、CD147亦存在相互作用；3.HE4存在岩藻糖基化修饰；4.HE4影响卵巢癌生物学行为可能通过ANXA2介导；5.芯片结果：HE4 影响MAPK及FAK通路相关分子表达。结合其他研究结果（ANXA2与S100A10、CD147等相互作用促进恶性肿瘤进展）推测：HE4与ANXA2是配-受体关系，HE4与ANXA2、S100A10、CD147等形成蛋白复合体，ANXA2在其中起"桥梁"作用；HE4与ANXA2结合对卵巢癌生物学影响与MAPK及FAK通路相关；HE4糖基化影响上述过程。本项目拟进一步阐明HE4与ANXA2的相互作用及其对卵巢癌发生发展的影响及机制。

Human epididymis protein 4 (HE4) is one of the ovarian cancer markers with the highest sensitivity and specificity by far, but most of the current researches focus on its application on the diagnosis, follow-up and prognosis for ovarian cancer as a biomarker, its mechanism on malignant tumor is still unknown. Our recent studies found that: (1) mass spectrometry analysis found that HE4 can combine with a protein named annexin A2 (ANXA2) with known structure; (2) fucose glycosylation presents on the surface of HE4 protein; (3) HE4 can interact with S100, CD147 protein; (4) HE4 can affect the biological behaviors of ovarian cancer mediated by ANXA2; (5) gene chip study prompted that HE4 can influence the expression of a plurality of signal molecules such as MAPK, FAK, etc. In consideration of the other researchers' findings that ANXA2 can promote the development of malignant tumors by interacting with multiple proteins such as S100 family, CD147, P-gp, we speculate that HE4 is a receptor of ANXA2, and it may form a protein complex with ANXA2, S100 family, CD147 to mediate the biological behaviors of ovarian cancer, ANXA2 may act as a " bridge" role in the HE4-ANXA2- protein complexes, the influence mechanism of the combination of HE4 and ANXA2 on the biological behaviors of ovarian cancer is related with MAPK and FAK signal pathways . The glycosylation of HE4 can further influence on the above processes. This project intends to clarify the interaction of HE4 and ANXA2 and their influence and mechanism on the occurrence and development of ovarian cancer.