循环肝癌干细胞异质性研究及其在肝癌转移复发中的作用

我们前期研究发现，肝癌患者外周血中存在具有干细胞特性的循环肝癌干细胞（Circulating Liver Cancer Stem Cells，CLCSC）并与肝癌预后密切相关。CLCSC具有明显的异质性，不同分子标志及治疗时间节点的CLCSC表型有着显著差异，其内在机制及临床意义不明。本课题将在大量前期工作基础上1）开发及优化基于免疫磁珠微流控芯片技术的新型CLCSC分选系统；2）筛选及鉴定不同分子标志及节点CLCSC，分析其与肝癌预后的相关性；3）利用单细胞转录组扩增测序技术，筛选CLCSC特征性基因表达谱及相关活化分子信号通路并明确鉴定，结合临床基因芯片数据库得到术后复发预测特异性分子标签；4）研究可特异针对肿瘤干细胞的纳米药物NanoHHI对CLCSC的作用及其机制。通过本研究可初步阐明CLCSC的异质性分子机制及其在肝癌转移复发中的作用，为临床提供新的肝癌复发预测手段及干预策略。

We screened circulating liver cancer stem cells（CLCSC）from most of the patients with Hepatocellular Carcinoma (HCC) and found its close relationship with the prognosis of those patients in our previous study, while the heterogeneity of CLCSC and its clinical significance were still ambiguity. In this study, we plan to 1) Develop and modify a new CLCSC screen system based on immunomagnetic beads microfluidic chip.2）Investigate CLCSC with different stem-cell markers, and from different time zone of treatments, and then analyses the relationship with the clinical characteristics. 3）Explore gene expression profiling of CLCSC and develop a new recurrence gene signature based on Single-Cell genomics system. 4) Reveal the effects of NanoHHI on CLCSC and its mechanism. In summary, a noval stratagem to predict HCC recurrence and metastasis and a new intervention method are expectable from this study.