晚期糖基化终末产物（AGEs）及其受体（RAGE）与子宫内膜癌的关系研究

糖尿病是公认的子宫内膜癌发病的高危因素，目前认为晚期糖基化终末产物（AGE）作为内环境异常糖代谢所堆积的产物可以导致糖尿病的"代谢记忆"，而这种体内糖代谢异常导致的内环境异常在致瘤作用中也是不容忽视的。我们在前期研究中发现AGE及其受体RAGE可能与子宫内膜癌的发生相关。本项目拟从代谢性疾病的角度研究子宫内膜癌的发病机制：首先探明患者血清中的AGE水平变化是否是子宫内膜癌的发生相关因子，进一步分析其表达水平是否与子宫内膜癌恶变程度相关；其次，分析AGE/RAGE系统在子宫内膜癌发生中的具体作用及机制；最后尝试干预AGE/RAGE的功能观察是否可以抑制子宫内膜癌细胞的恶性表型。这些工作的完成可能有助于形成以防治糖尿病为靶点，以降低子宫内膜癌患病率和病死率为首要目标的多危险因素综合防治的新策略，为临床诊治子宫内膜癌提出新的思路。

Endometrial cancer is the most common gynecologic malignancy and is strongly associated with diabetes and hyperglycemia. There is a growing body of evidence that advanced glycation end products (AGE) could induce the metabolic memory, which is involved in the development and progression of cancers. In our previous study, we found that AGE and the receptor for advanced glycation end-products (RAGE) was associated with endometrial cancer. In the present project, we will study the role of AGE/RAGE axis in the development and progression of endometrial cancer. The following question will be answered：1) Whether the serum levels of AGE in patients with endometrial cancer are associated with endometrial cancer and what is its potential clinical relevance; 2）the detailed mechanism of AGE/RAGE axis in the proliferation, metabolism and angiogenesis; 3) Whether the development and progression of endometrial cancer is inhibited by the blockage of AGE/RAGE axis in mice model. These works are necessary to find the novel therapeutic strategy for endometrial cancer ultimately leading to the decrease of the incidence and mortality rates for endometrial cancer.