Elafin通过EGFR/ERK信号通路调控肝细胞癌侵袭转移的机制研究

肝细胞癌侵袭转移是肝癌切除术后复发的主要原因。我们前期通过全基因组甲基化芯片发现 PI3基因（Elafin）甲基化与早期肝癌术后复发相关；进一步预实验发现EGFR可能是Elafin的潜在受体；干扰Elafin可激活EGFR/ERK并促进肿瘤细胞增殖、侵袭和上皮间质转化；肝癌细胞经去甲基化药物处理可上调Elafin的表达。本项目拟通过体外体内实验进一步研究Elafin对肝癌细胞侵袭转移的影响；探讨Elafin与EGFR的相互作用、Elafin通过EGFR/ERK信号通路抑制肝癌侵袭转移的分子机制；研究调控PI3的转录因子以及PI3启动子甲基化对其调控的影响；探讨肝癌组织及术前血清中Elafin的表达水平与患者临床病理特征和预后的相关性。本研究将阐明Elafin调控肝癌侵袭转移的机制，有助于预测肝癌术后复发风险，对指导肝癌个体化精准治疗具有重要的临床意义。

The invasion and metastasis of hepatocellular carcinoma (HCC) is responsible for high recurrence after tumor resection. Our previous study showed that PI3 gene (Elafin) CpG methylation assisted in predicting recurrence for early-stage HCC patients after resection. EGFR might be the receptor of Elafin. Downregulation of Elafin enhanced HCC cell proliferation, invasion and epithelial-mesenchymal transition by phosphorylation of EGFR and ERK. The expression of Elafin was up-regulated after demethylation treatment in HCC cells with PI3 methylation. In this project, we will study the role of Elafin in HCC cell invasion and metastasis in vivo and in vitro; and investigate the role of Elafin in EGFR/ERK signaling pathways. We will screen PI3 transcription factors and analyze whether PI3 expression could be regulated by DNA methylation. In addition, we will study the correlation of Elafin expression in neoplastic tissues and serum of early-stage patients with clinicopathological factors and prognosis. Our studies will help to understand the role of Elafin in HCC invasiveness and provide the recurrence risk prediction and personalized precise treatment for HCC patients.