原发性肝癌是消化系统最常见的恶性肿瘤之一，由于其具有化疗高度耐药、进展迅速以及复发率高等特点，因此至今仍缺乏有效的系统治疗方案。新近的研究发现Hippo-YAP通路在恶性肿瘤的发生发展过程中发挥着重要的作用，YAP蛋白在人结肠癌、胃癌、非小细胞肺癌以及卵巢癌等恶性肿瘤中高表达，并与临床预后成显著负相关，然而关于Hippo-YAP通路在原发性肝癌方面的研究则十分有限，特别是Hippo-YAP通路是否在肝癌化疗耐药方面发挥作用尚属未知。本课题在前期研究中发现YAP 在胆管细胞型肝癌组织中呈高表达，而在癌旁组织中低表达；肝癌细胞经化疗药物干预，YAP表达明显上调。因此，我们推测Hippo-YAP通路在原发性肝癌的防治，尤其是化疗耐药调控方面可能发挥着重要的作用。本项目将进一步明确Hippo-YAP通路在原发性肝癌发生发展以及化疗耐药方面的调控作用，有望为肝癌的系统治疗提供新的治疗靶点和干预手段。

Primary liver cancer is one of the most common malignant tumors of the digestive system. Because it's characterized with notoriously high chemoresistance, fast progression and high recurrence rate, the effective systemic therapy strategy is still limited. Recent studies show that Hippo-YAP pathway plays an important role in cancer development and progression, YAP protein is expressed at higher levels in the tissue of human malignant tumors such as colon cancer, stomach cancer, non-small cell lung cancer and ovarian cancer, etc. Significant inverse correlation was proved between its expression and the prognosis. However, studies on the role of Hippo-YAP pathway in primary liver cancer are limited, especially in the chemotherapy resistance of liver cancer is still unknown. In our previous study, it shows that the expression of YAP is highly expressed in the tissue of cholangiocellular carcinoma, as compared with the matched adjacent nonmalignant tissue; the expression of YAP is upregulated during the treatment of drugs in the cells of liver cancer. Therefore, we suppose that Hippo-YAP pathway may play an important role in the prevention and therapy of primary liver cancer, especially in the regulation of chemoresistance. This study is designed to test such hypothesis.