循环肿瘤细胞（circulating tumor cell，CTC）释放是肝癌转移复发的关键步骤，肿瘤微环境在此过程中扮演重要角色。我们经前期工作发现肝癌微环境中骨髓来源抑制性细胞（myeloid-derived suppressor cell，MDSC）的含量与外周CTC水平呈正相关；MDSC来源外泌体中miR-4295含量升高，并通过调控其潜在靶标ARHGAP24促进CTC的释放。此外，我们还发现血浆外泌体miR-4295检测在肝癌中具有潜在的临床价值。本研究拟在此基础上运用“活体流式”CTC检测技术、体内外肿瘤细胞功能实验联合临床队列研究，阐明miR-4295/ARHGAP24轴影响CTC释放及肝癌肿瘤生物学效应的具体作用，通过临床队列评估血浆外泌体miR-4295作为肝癌预后标志物的应用价值，探索通过外泌体抑制CTC释放及肿瘤转移的效果，为肝癌转移复发的防治提供新思路和转化依据。

The releasing of circulating tumor cell (CTC) represents the key process of the metastasis and recurrence of hepatocellular carcinoma (HCC), in which the tumor microenvironment plays a vital role. Our previous work has verified the numerical relationship between in-situ myeloid-derived suppressor cells (MDSC) and CTCs. MDSCs-derived exosomes carry abundance miR-4295 and promote the invasion of HCC with the cooperation of its targeted gene, ARHGAP24. Furthermore, we have revealed the potential utility of plasma exosomal miR-4295 in clinical practices. Based on these previous findings, we aimed to systematically investigate the role of miR-4295/ARHGAP24 axis in promoting CTCs releasing as well as in modulating the tumor characteristics and to clarify the detailed functions through flow cytometry assay for CTCs in vivo, tumor cellular functional assays together with clinical cohort analysis. The application of plasma exosomal miR-4295 as a novel HCC biomarker and the effects in inhibiting CTC releasing and metastasis of HCC by targeting MDSCs-derived exosome will be further evaluated. Our investigation would provide new insights into the prevention of HCC metastasis and recurrence.