缺氧微环境下PCDH20/IL-6/STAT3信号轴通过增强肝癌细胞干性促进TACE术后复发的机制研究

缺氧微环境下肿瘤细胞干性增强是肝癌TACE术后复发的重要原因。IL-6/STAT3信号通路与肿瘤细胞干性密切相关。申请人前期发现HCC患者TACE术后IL-6水平明显升高，是预后不良的独立危险因素。通过组织芯片及生信工具发现PCDH20极有可能是IL-6/STAT3通路的调控靶点。进一步的细胞实验表明，缺氧环境下PCDH20表达下调，而过表达PCDH20可抑制IL-6/STAT3号通路降低肝癌细胞干性。因此，我们提出：缺氧环境下PCDH20/IL-6/STAT3信号轴通过增强肝癌细胞干性促进TACE术后复发，但具体分子机制尚未阐明。鉴于此，本研究拟从体内外水平探讨TACE术后缺氧微环境下PCDH20/IL-6/STAT3介导肝癌细胞干性促进肿瘤复发的具体分子机制，并进一步分析上述关键基因表达水平与TACE临床疗效的关系。本研究有望从干细胞层面为提高TACE远期疗效提供新的思路与策略。

Enhanced stemness of hepatoma cells under hypoxia microenvironment is the main reason for the recurrence of hepatocellular carcinoma (HCC) after TACE. IL-6 / STAT3 signaling pathway plays an important role in regulating the stemness of hepatoma cells. Our previous studies found that IL-6 level was significantly increased after TACE, which is an independent risk factor for poor prognosis. We found that Protocadherin 20 (PCDH20) is very likely to a regulator of the IL-6/STAT3 signaling pathway via tissue chip and bio-information analysis tools. Cell function experiments furtherly showed that PCDH20 was down-regulated under hypoxia microenvironment. Overexpression of PCDH20 can reduce the stemness of HCC cells by down-regulating IL-6 / STAT3 signaling pathway. Therefore, it is reasonable to speculate that PCDH20 / IL-6 / STAT3 signal axis promotes the recurrence of HCC after TACE by enhancing the stemness of HCC cells under hypoxic environment, but its molecular regulatory mechanism has not been elucidated. In view of this, this study intends to explore the specific regulatory mechanism of PCDH20/ IL-6 / STAT3 pathway on the stemness of hepatoma cells under hypoxia microenvironment in vivo and in vitro, and furtherly analyze the relationship between the expression level of these key genes and the clinical efficacy of TACE. This study is expected to provide new ideas and strategies for improving the long-term efficacy of TACE from the stem cell level.