肝癌的发病率与死亡率逐年增高，早期诊断与实时监测对于肝癌的防控意义重大。研究发现，肝癌患者外周血中存在着极微量的循环肿瘤DNA，与肿瘤的发生发展及预后具有密切关系。然而，目前循环肿瘤DNA检测主要依赖于测序，不便于临床广泛开展且其尚未对循环肿瘤DNA富集而难以准确检测。研究表明，TP53 R249S是肝癌基因突变的标志性位点，且与黄曲霉素诱导肝癌的形成及肝癌预后具有显著相关性。本研究拟在前期研究基础上将TP53 R249S作为肝癌循环肿瘤DNA的生物标签，自主设计特异性富集TP53 R249S突变型基因的锁核酸探针及引物对；建立TP53 R249S生物标签的循环肿瘤DNA检测体系，并对上述体系与条件进行优化；然后对检测体系的灵敏度等性能指标进行评价，并利用临床标本进行验证。本研究不仅为肝癌的临床超早期诊断与实时监测提供一项重要的检测技术，同时为肝癌致病因素及患者预后提供重要的参考依据。

The incidence and mortality of HCC is increasing year by year. Early diagnosis and real-time monitoring is of great significance for prevention and control of HCC. The study found that there is a very small amount of circulating tumor DNA in the peripheral blood of patients with HCC, which is closely related to the occurrence and development of tumor. However, DNA detection of circulating tumor is mainly dependent on sequencing, which is not easy to be widely carried out and it has not yet been detected in circulating tumor DNA. The study showed that R249S TP53 was the marker of liver cancer gene mutation, and it had significant correlation with the formation of liver cancer and the prognosis of HCC. This study intends to make R249S TP53 as the biomarker of liver cancer circulating tumor DNA in the biological labels on the basis of the preliminary study, and design LNA probes and primers to enrich R249S TP53 mutant gene; establish the detection system of R249S TP53 biological labels of circulating tumor DNA, and the optimize of the system and conditions; then evaluate the sensitivity of the detection system, and use the clinical specimens are to verify the accuracy of the new detection technology. This study not only provides an important detection technology for the early diagnosis and real-time monitoring of liver cancer, but also provides an important data for the risk factors and prognosis of patients with liver cancer.