TACC3介导肝癌射频消融治疗后转移复发的机制及干预策略

射频消融（RFA）是小肝癌的根治性治疗手段之一，但部分患者消融术后容易发生转移/复发，具体机制尚不明确。我们的前期研究发现TACC3在肝癌细胞高表达，与患者预后差显著相关；临床样本和小鼠模型均显示不完全RFA肝癌组织中TACC3的表达显著增高，初步的机制研究表明TACC3能诱导肝癌细胞上皮间质转化（EMT）。因此，我们提出RFA治疗后引起肿瘤组织TACC3表达上调，促进肝癌细胞EMT发生，进而导致肿瘤转移/复发的假说。以此为基础，本研究拟利用小鼠肝癌RFA治疗模型、体外实验和临床样本：1）明确TACC3与RFA治疗后EMT发生的关系；2）深入阐明RFA引起TACC3表达的原因以及TACC3参与治疗后转移发生的具体调控机制；3）探讨阻断TACC3以及联合靶向药物预防RFA治疗后转移/复发的临床可行性。所得结果有望揭示肝癌RFA治疗后发生转移/复发的新机制，为肝癌的临床治疗提供新的靶标和依据。

Radiofrequency ablation (RFA) is one of the radical treatment of small hepatocellular carcinoma (HCC), while some patients are prone to recurrence/metastasis after ablation, the mechanism is not clear. Our previous study found that TACC3 expression and clinical outcome of patients with HCC was significantly negatively correlated. Clinical samples and mouse model showed TACC3 was over-expressed elevated after RFA. Preliminary study found that TACC3 could up-regulate proteins related to epithelial mesenchymal transition (EMT). We hypothesized that RFA may induce the upregulation of TACC3 expression, and promote the occurrence of EMT in HCC cells, which led to the recurrence and metastasis. In this project, we intend to employ RFA model of hepatocellular carcinoma in mice, in vitro and clinical samples to study: 1) relation between TACC3 and EMT occurrence after RFA of HCC; 2) clarify how TACC3 get over-expressed by RFA and its specific regulation mechanism on metastasis after RFA. 3) to explore the clinical feasibility whether inhibition of TACC3 and combination with target therapy could prevent metastasis/recurrence after RFA. The results are expected to reveal a new mechanism of recurrence and metastasis of HCC after RFA treatment, and provide experimental evidences and a new clue to TACC3 targeting therapy for HCC.