干细胞因子SALL4在卵巢癌发生发展及判断预后中的作用

项目名称： 干细胞因子SALL4在卵巢癌发生发展及判断预后中的作用

项目编号： No.81472029

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 崔巍

作者单位： 中国医学科学院北京协和医院

项目金额： 65万元

中文摘要： 卵巢癌死亡率高居妇科肿瘤首位，对卵巢癌发生发展分子机制的研究有助于早期诊断和治疗，从而改善预后。染色体20q12-q13区域扩增常见于卵巢癌，而干细胞因子SALL4定位于染色体20q13.13-q13.2，可能是卵巢癌这一区域扩增的靶基因之一。本课题组和合作者在近8年的研究中，发现SALL4是白血病和骨髓异常增生综合征（MDS）的致病基因，SALL4在MDS的预后判断中具有潜在的监测意义。而SALL4在卵巢癌发生发展中的作用及其表达模式尚未见报道。为此，本课题拟从动物和细胞水平，通过SALL4功能缺失和获得性试验，探讨SALL4如何通过信号传导通路调节卵巢癌细胞的生长发育的增殖分化；同时，从临床角度，借助本课题组已建立的循环肿瘤细胞（CTCs）检技术，动态分析CTCs中SALL4的表达和功能，进一步探讨SALL4是否具有卵巢癌CTCs的干细胞活性，及其在卵巢癌疗效评价和预后判断中的作用。

中文关键词： 干细胞因子；SALL4；卵巢癌；分子标志物；循环肿瘤细胞

英文摘要： Ovarian cancer is the leading cause of death from female reproductive tract malignancies. Dissecting molecular pathways underlying tumor initiation and maintenance of the ovarian cancer can provide early detection and new prevention strategies. The chromosomal region, 20q12-13, is commonly amplified in ovarian cancer, which suggests that the genes amplified within that region may play a central role in the tumor initiation of ovarian carcinoma. The human SALL4 gene is located on chromosome 20q13.2. We hypothesize that SALL4 is an important candidate gene of the 20q12-q13 amplicon that plays an essential role in ovarian cancer initiation. Our research team and partners has worked on SALL4's role in human cancers for the last eight years. We have first reported that SALL4 is an novel oncogene for MDS and AML and our recent finding suggest that SALL4 has potential role in the prognosis of MDS. However, the expression pattern and clinical application of SALL4 in ovarian cancer have not been reported yet. In this study, we will dissecting the mechanism of SALL4 in the initiation and maintenance of the ovarian cancer by both gain of function and loss of function studies in celllines and mouse model. One the other hand, we will use circulating tumor cells (CTCs) as a new platform which is well established in our lab to investigate wether CTCs with SALL4 exprssion is functioned as the cancer stem cell and further evaluate the clinical application of SALL4 in predicting prognosis and monitoring treatment of ovarian cancer.

英文关键词： Stem Cell Factor;SALL4;Ovarian Cancer;Molecular Marker;Cirtulating tumor cell