染色体杂合性缺失（LOH）筛查是寻找抑癌基因的一种有效手段，5p15.3是本项目组前期在胃癌研究中原创性发现的高频LOH位点。我们已就该位点的候选抑癌基因IRX1进行了一系列功能分析，明确了该基因的抑癌功能特性，研究成果获国际同行认可，并作为重要证据录入NCBI基因数据库。当前，基因数据库内登录有数万条人类基因，但相当一部分基因的确切生物学功能尚不清楚，5p15.3位点内的另一候选抑癌基因NKD2便属此类。NKD2在克隆初期被认为是Wnt信号通路的负性调控因子，但新近有研究提示其还参与其他重要功能蛋白的调控。NKD2在胃癌发生发展中的分子机制尚缺乏系统性研究。本研究从DNA水平、mRNA转录、蛋白表达、NKD2的基因过表达及转染细胞的裸鼠成瘤性与转移能力等多角度探讨NKD2基因与胃癌的关系，最终探明NKD2在胃癌发生发展中的确切作用机制，为开发胃癌诊治中的新型分子靶点提供源头数据。

Screening loss of heterozygosity (LOH) in chromosome is an effective means of finding tumor suppressor genes. 5p15.3, a target region with high frequency of LOH is originally found in the analysis of gastric cancer by our group. Under the supporting of National Natural Science Foundation of China, we focused on candidate gene IRX1 and performed a series of functional studies. We firstly characterized the tumor suppressor functions of IRX1, which have been approved as important evidence of tumor suppressor gene by international peers. Our previous results have been inputted into NCBI database entries. Currently, thousands of human genes are recorded in database. However, the exact biological function of these genes is unclear yet, pending in-depth study. NKD2 is such a gene, located in 5p15.3 LOH locus. NKD2 is originally considered a negative regulator of Wnt signaling pathway. But recent research suggests that it may also involve in interaction with other important functional protein. Up-to-date, it lacks of systematic research for NKD2 molecular mechanism in gastric cancer. This study will focus on NKD2 gene and its relationship with gastric cancer. We will analysis the genomic alteration, mRNA transcription and protein expression of NKD2 gene. We also evaluate the biological effects based on NKD2 gene transfection in vitro. The tumorigenesis and invasive ability will be studied by nude mice experiments. The purpose of the project is to clarify the exact mechanism of NKD2 on regulating carcinogenesis and development of gastric cancer, and develop novel molecular targets for diagnosis and treatment of gastric cancer.