Predictive value of intratumour inflammatory cytokine mRNA levels of hepatocellular carcinoma patients and activation of two distinct pathways govern IL-8 induced epithelial-mesenchymal transition in human hepatic cancer cell lines
Predictive value of intratumour inflammatory cytokine mRNA levels of hepatocellular carcinoma patients and activation of two distinct pathways govern IL-8 induced epithelial-mesenchymal transition in human hepatic cancer cell lines
复制标题
肝细胞癌患者肿瘤内炎症细胞因子 mRNA 水平的预测价值以及两种不同途径的激活控制人肝癌细胞系中 IL-8 诱导的上皮间质转化
DOI：
10.1016/j.cyto.2019.03.012
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发表时间：
2019-07-01
期刊：
影响因子：
3.8
通讯作者：
Zeng, Linjuan
中科院分区：
文献类型：
--
作者：
Peng, Siqi;Chen, Yutong;Zeng, Linjuan
肝细胞癌（Hepatocellular carcinoma，HCC）常伴有肝组织的持续性炎症反应，炎症反应通过促进肿瘤的生长、发展和转移而发挥促癌作用。然而，肿瘤内炎性细胞因子的促肿瘤作用和预测价值仍不清楚。在本研究中，我们使用数据库分析，临床病理学研究和体外生物学实验对人肝癌细胞系，以评估原发性肿瘤细胞因子mRNA水平的预后潜力和HCC的潜在机制。首先，我们从TCGA数据库中评估了几种细胞因子的预后价值，发现IL-8是一种独特的细胞因子，与HCC患者的总生存率低相关。然后，我们收集了87例患者的HCC肿瘤和邻近非肿瘤标本，并证实与IL-8高表达的患者相比，IL-8低表达的患者表现出较少的肝内浸润或远处转移，较低的复发率和较长的总生存时间。创伤愈合、transwell和western blotting实验结果表明，IL-8促进Huh-7和HepG 2细胞的迁移和侵袭，其机制是通过IL-8/ERK 1/2/SNAI 1和IL-8/STAT 3/TWIST 1信号通路诱导肝癌细胞EMT。这些结果为肝癌靶向治疗研究提供了有价值的IL-8生物学信息。此外，肿瘤内细胞因子在mRNA水平上的表达可以提供对肝癌预后的洞察。
Hepatocellular carcinoma (HCC) is always accompanied by persistent inflammation of liver tissues, which is considered to exert protumourigenic effects by promoting cancer growth, progression, and metastasis. However, the tumour-promoting roles and predictive value of intratumoural inflammatory cytokines remain unclear. In the present study, we used database analysis, clinical pathological studies, and in vitro biological experiments on human hepatic cancer cell lines to assess the prognostic potential of the primary tumour cytokine mRNA levels and underlying mechanisms in HCC. First, we assessed the prognostic value of several cytokines from the TCGA database and found that IL-8 is a unique cytokine that is associated with poor overall survival of HCC patients. Then, we collected 87 HCC tumour and adjacent non-tumour specimens from patients and confirmed that patients with low IL-8 expression exhibited less intrahepatic invasion or distant metastasis, a lower recurrence rate and longer overall survival time compared to patients with high IL-8 expression. Wound healing, transwell, and western blotting assay results showed that IL-8 promotes the migration and invasion of Huh-7 and HepG2 cells, and the underlying mechanism is that IL-8 induces the EMT of HCC cells via the IL-8/ERK1/2/SNAI1 and IL-8/STAT3/TWIST1 signalling pathways. These results provide valuable biological IL-8 information which needs to be further investigated in liver cancer target therapy research. Furthermore, the intratumoural cytokine expression at the mRNA level may provide insight into hepatocarcinoma prognosis.