外周血循环肿瘤DNA突变谱用于肝癌早期诊断及改善预后的研究

项目名称： 外周血循环肿瘤DNA突变谱用于肝癌早期诊断及改善预后的研究

项目编号： No.81502593

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： 孙岩

作者单位： 深圳华大生命科学研究院

项目金额： 18万元

中文摘要： 癌症的有效预防与治疗一直是困扰着现代医学的一个难题。近年来我国癌症发病率和死亡率持续上升，人们迫切需要一种有效的方法对肿瘤的进展以及预后进行有效的监测。随着测序技术的发展，循环肿瘤DNA作为一种高敏感性和特异性的肿瘤标志物在肿瘤早期预测以及预后监测等方面表现出非常大的潜力。本项目创新性地采用靶向测序技术对肝癌循环肿瘤DNA的突变谱进行相关分析，以期阐明这种方法在研究肿瘤特性等方面的可行性，以及在检测、监测和癌症早期预测方面的效用。研究选取肝癌作为研究对象，通过创新的算法设计与肝癌相关的特异性芯片，对目标区域进行捕获；随后进行高通量测序，通过生物信息学的方法对肝癌患者的循环肿瘤DNA水平、特征性基因改变等进行分析，为肿瘤的早期诊断、疗效评估、复发监测及预后判断提供重要信息。与传统活检相比，肿瘤循环DNA的检测可以提供更全面的癌症信息，对于肿瘤早期诊断及改善预后有重要意义。

中文关键词： C09_肝和肝内胆管肿瘤；循环肿瘤DNA；高通量测序；生物标志物；癌症预后

英文摘要： The prevention and treatment of cancer has always been a huge problem in modern medicine. In recent years, the morbidity and mortality of cancer patients continued its remorseless rise in China, there is an urgent need to develop an effective method to monitor tumor dynamics and measure tumor burden. With the development of sequencing technology, circulating tumor DNA (ctDNA) has been recognized as a specific and highly sensitive biomarker. In this project, in order to illustrate the role of ctDNA in cancer detection, monitoring and early prediction, we aim to develop a new method here, we plan to perform targeted next-generation sequencing to analyze patient specific mutation sites. First, we aim to employ a novel algorithmic approach to design a custom chip covering all the liver cancer related genes; then, we plan to use deep sequencing, bioinformatics and statistical methods to identify specific somatic mutations in patients with liver cancer. We would examine whether significantly detectable levels of ctDNA reflect tumor dynamics, clinical responses to therapy, and prognosis. Compared to traditional biopsy, the detection of ctDNA could provide more information of human liver cancer, which is essential for cancer early diagnosis and may improve the prognosis.

英文关键词： liver cancer and intrahepatic cholangiocarcinoma;ctDNA;next-generation sequencing;biomarker;prognosis of cancer