21q21.3遗传多态性影响CYYR1并促进肝细胞癌发生、发展的相关机制及临床应用价值研究

课题组的前期研究发现肝细胞癌患者21q21.3区域存在遗传多态性，它们影响肝细胞癌的发病风险，本课题的预实验进一步发现，该区域显性单核苷酸多态性（SNP）影响CYYR1的表达，但其具体调控机制及作用并不清。本课题将以此为线索，开展如下研究：(1)采用回顾性病例对照研究方式研究与分析21q21.3区域显性SNP对肝细胞癌发病及预后的影响；（2）通过临床病理学技术研究与分析这种显性SNP对CYYR1表达的影响；（3）通过细胞生物学及分子克隆技术研究该区域显性SNP与CYYR1表达间的调控机制，分析这种机制在肝细胞癌发生和发展进程中的作用；（4）通过体内实验与临床样本研究分析这种调控机制的临床应用价值。以上研究将首次阐述21q21.3区域遗传多态性与CYYR1间调控机制以及这种机制在肝细胞癌发生发展中的作用，有助于进一步阐明肝细胞癌发生发展的相关机制，对肝细胞癌的防治提供新的重要科学数据支持。

Our previous studies have shown that the genetic polymorphisms in the 21q21.3 region affect the risk of hepatocellular carcinoma (HCC); whereas through the prepare experiment, we found that significant single nucleotide polymorphisms (SNPs) modified the expression levels of CYYR1 gene. However, its mechanism is unclear. Based on the aforementioned facts, we plan to investigate the following research: (1) investigating and analyzing effects of significant SNPs in the 21q21.3 region on the risk and prognosis of HCC via a retrospective hispital-based case-control study; (2) exploring and analyzing effects of significant SNPs in the 21q21.3 region on CYYR1 expression using pathological method; (3) researching the modificative association between significant SNPs in the 21q21.3 region and CYYR1 expression using cellular and molecular biology techniques, and role of this mechanism in the carcinogenesis and progress of HCC; and (4) analyzing the clinic values of significant SNPs in the 21q21.3 region modifying CYYR1 expression. The present project would help us not only to firstly elucidate the molecular mechanisms of genetic polymorphisms in the 21q21.3 region and CYYR1 expression, and the role of this modified mechansim in the carcinogenesis and progress of HCC, but to provide new important experimental data for prevention and treatment of HCC.