Role of Matrix Metallopeptidase 12 in the Development of Hepatocellular Carcinoma
Role of Matrix Metallopeptidase 12 in the Development of Hepatocellular Carcinoma
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基质金属肽酶 12 在肝细胞癌发生中的作用
DOI：
10.1080/08941939.2019.1637975
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发表时间：
2019-07-15
影响因子：
1.9
通讯作者：
Lu, Jun
中科院分区：
文献类型：
--
作者：
Gao, Hengjun;Zhou, Xu;Lu, Jun
摘要 目的探讨基质金属肽酶12（MMP-12）在肝细胞癌（HCC）发生发展中的作用。材料与方法：对 343 例 HCC 患者进行回顾性分析。采用免疫组织化学染色法检测MMP-12表达，并分析MMP-12表达与临床特征的相关性。采用酶联免疫吸附试验（ELISA）检测血清白介素6（IL-6）和IL-10水平。采用Kaplan-Meier法进行生存分析，并通过流式细胞仪检测T细胞中PD-L1的表达。结果：HCC 组织中 MMP-12 的表达与年龄、性别、病毒感染、肝硬化、Child-Pugh 评分、甲胎蛋白水平或巴塞罗那临床肝癌分期没有相关性。然而，较高水平的MMP-12表达与肿瘤大小增加、肿瘤细胞分化较差、TNM分期较高和预后较差相关。此外，MMP-12的表达与PD-L1的表达呈正相关。进一步分析表明MMP-12对PD-L1表达的调节可能通过IL-6信号通路发生。结论：MMP-12 表达水平较高表明预后较差。 PD-L1表达与MMP-12表达呈正相关，提示MMP-12可能通过上调PD-L1促进HCC的发生发展。
Abstract Objective The aim of this study was to investigate the role of matrix metallopeptidase 12 (MMP-12) in the development of hepatocellular carcinoma (HCC). Materials and Methods : A total of 343 HCC patients were retrospectively analyzed. MMP-12 expression was detected by immunohistochemical staining and the correlation between MMP-12 expression and clinical features was analyzed. Serum interleukin-6 (IL-6) and IL-10 levels were detected by an enzyme-linked immunosorbent assay (ELISA). Survival analysis was performed using the Kaplan–Meier method and PD-L1 expression in T cells was detected by flow cytometry. Results : MMP-12 expression in HCC tissues showed no correlation with age, gender, viral infection, cirrhosis, Child-Pugh score, alpha-fetoprotein levels, or Barcelona-Clinic Liver Cancer stage. However, higher levels of MMP-12 expression were correlated with increased tumor size, poorer tumor cell differentiation, higher TNM stage, and poorer prognosis. Moreover, MMP-12 expression was positively correlated with PD-L1 expression. Further analysis indicated that the regulation of PD-L1 expression by MMP-12 may occur through the IL-6-signaling pathway. Conclusions : Higher levels of MMP-12 expression indicated a poorer prognosis. PD-L1 expression was positively correlated with MMP-12 expression, indicating that MMP-12 may promote the development of HCC through the up-regulation of PD-L1.