甲状腺癌TERT 启动子突变与剪切波弹性成像的相关性及机制研究

项目名称： 甲状腺癌TERT 启动子突变与剪切波弹性成像的相关性及机制研究

项目编号： No.81501475

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 徐军妹

作者单位： 同济大学

项目金额： 18万元

中文摘要： TERT启动子突变是目前所发现与滤泡来源的高侵袭性甲状腺癌（TC）相关性最高的基因改变，其机制部分与肿瘤微环境（TME）中肿瘤细胞的侵袭性增强及细胞外基质的降解有关，而肿瘤组织的弹性取决于后者；剪切波弹性成像可反映组织弹性，我们前期研究发现，其不仅可鉴别诊断TC，也可预测TC的转移；据此提出假设，剪切波弹性成像可用于TC术前风险预测，其机制与TERT启动子突变及TME的改变有关。为验证该假设，本项目拟在前期工作基础上建立TC的TERT启动子干扰肿瘤模型，比较TERT启动子突变被干扰后TME和剪切波弹性成像的变化及小鼠肿瘤转移情况，研究TERT启动子突变及TME与剪切波弹性成像的相关性，探索剪切波弹性成像对TC进行预后预测的效能。本项目对从分子水平阐明剪切波弹性成像预测TC预后的作用有重要意义，有望建立一种TC术前风险预测的新模式。

中文关键词： 超声成像；剪切波弹性成像；甲状腺癌；TERT启动子

英文摘要： TERT promoter mutation was the strongest associated with the high invasive thyroid cancer (TC). And the mechanism partly related to changes in the tumor microenvironment (TME) with infiltrate tumor cells and extracellular matrix degradation (EMD). The elasticity of tumor tissue depends on EMD, and shear wave elastography (SWE) can reflect tissue elastography. Meanwhile, our previous studies showed that SWE not only could differentiate TC from benign thyroid nodules, but also could predict the prognosis of TC. Based on the above, we hypothesized that SWE could be used to assess the preoperative risk and predict the prognosis of TC, and the mechanisms were relative of the TERT promoter mutation and the changes of TME. We aimed to build a TERT promoter Ad-hTERT-TK-enh interference tumor model to compare the changes of TME and elastography parameters, and the tumor metastasis in the nude mice. Then, we focused on the study of the relationship between TERT promoter mutation, TME and SWE, and explore the mechanism of SWE in prediction of the prognosis of TC. This project is important to clarify the mechanism of SWE in prediction of the prognosis of TC at the molecule level. The project will provide a new mode for the preoperative risk assessment and prediction of the prognosis of TC.

英文关键词： ultrasound;shear wave elastography;thyroid cancer;TERT promoter