哈萨克族食管鳞癌相关基因THSD7A的下游驱动基因筛选、临床意义和功能研究

食管癌侵袭性强且预后极差，目前其发生发展的分子生物学机制仍不清楚。为研究其潜在致病因子，课题组采用外显子二代测序，首次发现凝血酶敏感蛋白1型7A基因（THSD7A）在哈萨克族食管鳞癌组织中突变率高达18.5%，明显高于同地区的维吾尔族。进一步的基因表达和功能实验显示，THSD7A与哈萨克族食管癌相关且可能是食管鳞癌的致癌基因。更深入的高通量芯片实验显示，THSD7A通过多个经典通路和下游新基因发挥作用。在前期研究基础上，本项目拟开展疑似THSD7A下游新基因的验证、筛选，进而在哈萨克族食管鳞癌组织、细胞和动物实验三个层面，运用克隆形成、RT-PCR、Western blotting等成熟实验技术，发现下游驱动基因，分析下游新基因的表达与哈族食管鳞癌恶性表型的关系，明确其在食管癌发生、发展中的功能，揭示下游驱动基因的临床意义和分子生物学功能，为哈族食管癌分子分型和个体化靶向治疗奠定基础。

As a malignant tumor, the esophageal cancer is aggressive and very poor prognosis. However, the molecular mechanism of etiology and pathogenesis is unclear now. In order to find the pathogenic gene, we use the second generation sequencing technology-sequencing the whole exome of Esophageal Squamous Cell Carcinoma(ESCC) in the Kazak and Uyghur ethnic. We have found that the mutation rate of THSD7A gene in Kazak ethnic(18.5%) is significantly higher than that in the Uyghur ethnic, which has racial differences. Further experiments on gene expression and function showed that THSD7A is associated with esophageal cancer and may be carcinogenic gene in ESCC. And more in-depth high-throughput chip experiments showed that THSD7A plays a role by several classical pathways and downstream genes. On the basis of previous research, this project is intended to carry out the verification and screening of new THSD7A downstream genes through a variety of mature experimental techniques(Clone formation experiment, RT-PCR, Western blotting, et al) from three aspects, in carcinoma tissue, cell and animal model. We want to analysis of the relationship between new downstream gene expression and malignant phenotype of Kazakh ESCC, and clarify its function in the occurrence and development of ESCC. So as to reveal the clinical significance and molecular function of the downstream driving gene, to lay the foundation for molecular classification and individual treatment of Kazakh ESCC.