USP44基因启动子甲基化在鼻咽癌增殖和放疗敏感性中的调控机制及其预后价值研究

TNM临床分期系统是制定鼻咽癌治疗策略的基础，然而同一分期内患者预后仍有较大差异，因此急需寻找有效的分子指标来提高鼻咽癌预后预测效能及指导个体化治疗。我们前期研究初步显示：①利用全基因组甲基化芯片和qPCR检测发现鼻咽癌组织中USP44基因高甲基化且表达减少，高甲基化的患者预后较差；②降低USP44在鼻咽癌细胞中的表达可以促进细胞增殖及放疗抵抗，但其具体功能及机制尚不清楚。本申请项目拟在此基础上：①检测350例鼻咽癌组织中USP44基因启动子区甲基化状态，研究其对鼻咽癌患者预后的预测价值；②在体内外模型中研究USP44基因在鼻咽癌增殖及放疗敏感性中的具体功能及机制。以此明确USP44基因甲基化对鼻咽癌患者预后的预测价值，阐明其在鼻咽癌中的功能及机制，为鼻咽癌个体化治疗提供新的治疗靶点。

Currently, TNM clinical stage remains the basement of clinical decision making for nasopharyngeal carcinoma (NPC) patients. However, sometimes patients with the same TNM clinical stage have different outcomes due to their individual heterogeneity. It is urgent to find out a molecular maker which can increase the ability of forecasting the prognosis and guide the individual treatment of NPC patients. In the previous study, we found that USP44 gene was significantly hypermethylated in NPC through screening the genome-wide methylation gene arrays, and patients with USP44 hypermethylation tend to have worse outcomes. In vitro, NPC cells grown faster and became more resistant to radiotherapy after knocking down USP44 expression, which suggest that USP44 may act as a tumor suppressor gene, but the mechanism is unknown. In this project, we will detect the USP44 methylation status of 350 NPC patients and examine its prediction value in NPC prognosis firstly. Then, we will study the function and mechanism of USP44 in vitro and in vivo. Through this research, it may provide a potential novel target for individual therapy in NPC patients.