基于肿瘤转移微环境（TMEM）理论探索ANG2-Tie2轴促进VETC型肝癌恶性进展的作用及机制研究

肝癌的高度异质性是肝癌精准医疗面临的最大挑战。对肝癌进行亚型分类并基于分型开展针对性的干预策略，是目前最富有前景的研究方向。最新研究发现，肝癌中存在一种高度恶性的血管病理类型，即血管包绕的肿瘤细胞团（VETC）。但是，VETC型肝癌恶性进展的调控及分子机制尚不明确。本课题基于肿瘤转移微环境（TMEM）理论，拟探讨肝癌细胞、Tie2高表达巨噬细胞（TEMs）及肿瘤内皮细胞（TECs）在TMEM中的相互作用，证实ANG2-Tie2轴调控TEMs参与VETC型肝癌恶性进展，阐明ANG2-Tie2轴调控VASH1-去酪氨酸化微管途径的分子机制及其在VETC血管生成中的作用，并进一步探讨应用Vanucizumab干预ANG2-Tie2轴对VETC型肝癌潜在的靶向干预价值。期待通过本课题的研究为抑制VETC型肝癌恶性进展提供新的线索及思路。

The high heterogeneity of hepatocellular carcinoma (HCC) is the biggest challenge for precise treatment of HCC.There is a pressing need to find new treatment strategies based on distinct subtypes of HCC.Recent studies found a special vascular pattern in HCC, the vessels that encapsulate tumor clusters (VETC), previously linked to HCC recurrence and metastasis. However, the molecular characteristics and the potential regulatory mechanisms of VETC pattern (VETC+) HCC are still poorly understood.Based on the theory of tumor microenvironment metastasis, this study aims to discuss the crosstalk between HCC cells, Tie2-expressing macrophages (TEMs) and tumor endothelial cells (TECs) as follows: a) To confirm the role of TEMs regulated by ANG2-Tie2 axis in malignant progression of VETC; b) To clarify the role and mechanism of VASH1-detyrosinated microtubules pathway egulated by ANG2-Tie2 axis in endothelial angiogenesis of VETC; c) To explore the effect of Vanucizumab on VETC+ HCC. In conclusion, this study are expected to provide new clues for inhibiting the malignant progress of VETC+ HCC.