肝癌介入栓塞后侵袭转移的增强是限制其疗效的瓶颈，迄今对这一现象的机制仍知之甚少。EGFL7是新发现的受缺氧调控的促转移基因，结构类似Notch通路受体功能区。我们的前期研究提示，肝癌患者介入栓塞后血清EGFL7显著升高，兔肝癌模型肝动脉栓塞（TAE）后EGFL7表达上调，EGFL7抗体阻断后肝癌细胞侵袭能力减弱。据此假说：肝癌TAE后EGFL7表达上调，促进其侵袭转移，Notch通路是重要的参与机制。为验证该假说，我们应用ELISA、实时定量PCR、Western blot从临床与基础、体内与体外研究TAE对肝癌EGFL7表达的影响。用慢病毒转染、RNA干扰调节人肝癌细胞EGFL7表达，适时阻断Notch通路，从分子、细胞、组织及整体水平研究EGFL7在肝癌侵袭转移中的作用，并探讨可能机制。本研究将从EGFL7这个新视点揭示肝癌介入栓塞后侵袭转移增强的现象与机制，为肝癌靶向治疗提供新思路。

Trans-catheter arterial chemo-embolization (TACE) is the main strategy for treatment of hepatocellular carcinoma (HCC) with BCLC stage B. However, enhancement of metastasis after TACE is the bottleneck to limit its effect. This is associated with several gene transcriptional activation induced by hypoxia due to TACE (mainly due to trans-catheter arterial embolization, TAE). Epidermal growth factor-like domain 7 (EGFL7) has been discovered recently as an angiogenesis factor, taking similar structure of Notch receptor area, but has been rarely reported in hepatocellular carcinoma. Our previous study found that patients with HCC treated with TACE showed increased transcription activation and expression of EGFL7 in peripheral blood, which is associated with tumor metastasis. The invasive and angiogenic capabilities are significantly weakened by EGFL7 antibody in HCC cells. Accordingly, we initiated the hypothesis: EGFL7 transcriptional activation occurs in HCC after TACE, and promotes the metastasis of HCC. Notch pathway is one of the possible mechanisms involved in this process. This project aims to investigate the influence of TAE on the expression of EGFL7 by observing the changes of EGFL7 protein from blood samples of HCC patients treated with TACE, and changes of EGFL7 mRNA and protein in pathological sections after TAE in animal models. With human HCC cell and animal models, using gene silencing and over-expression to target the regulation of EGFL7 expression in order to block the Notch pathway, this project also aims to explore the relationship between EGFL7 and metastasis of HCC generally on molecules, cellular, histic and animal levels. This project will provide theoretical and experimental basis for EGFL7 as a potential target for HCC gene therapy, which could be combined with TACE as a new comprehensive treatment for HCC patients.