CD146 promotes metastasis and predicts poor prognosis of hepatocellular carcinoma.
CD146 promotes metastasis and predicts poor prognosis of hepatocellular carcinoma.
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CD146促进肝细胞癌转移并预测不良预后
DOI：
10.1186/s13046-016-0313-3
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发表时间：
2016-02-29
期刊：
影响因子：
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通讯作者：
Wang X
中科院分区：
文献类型：
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作者：
Jiang G;Zhang L;Zhu Q;Bai D;Zhang C;Wang X
背景：肝细胞癌（HCC）是全球癌症相关死亡的第三大原因。根治性切除后的复发和转移仍然是HCC治疗的关键障碍。CD146可预测多种癌症的不良预后，包括黑色素瘤、乳腺癌、前列腺癌和胃癌。然而，CD146在HCC中的作用尚未得到系统的探讨。方法采用实时荧光定量PCR和western blotting （WB）技术检测CD146在肝癌组织和细胞系中的表达，探讨CD146在肝癌中的作用。其次，我们建立了稳定过表达和干扰CD146的HCC细胞系，并在体外和体内探索了CD146在HCC中的功能。第三，我们进行了微阵列分析，通过鉴定差异表达基因来研究潜在的机制。最后，我们进行了随访，以帮助揭示CD146表达与HCC患者预后的关系。结果我们发现CD146在HCC组织中过表达，CD146的高表达预示着HCC患者的总生存时间较差，复发期较短。体外和体内实验表明，CD146促进HCC细胞系的迁移和侵袭。进一步研究表明，CD146促进上皮间充质转化（epithelial mesenchymal transition， EMT）、IL-8上调和STAT1下调。CD146在HCC组织和细胞系中表达上调。结论scd146可促进肝癌细胞转移，预测肝癌患者预后不良。CD146诱导EMT， IL-8上调和STAT1下调可能是潜在的潜在机制。确切的机制还需要进一步研究。
BackgroundHepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. Recurrence and metastasis after curative resection remain critical obstacles in HCC treatment. CD146 predicted poor prognosis of a variety of cancers including melanoma, breast tumors, prostate cancer, and gastric cancer. However, the role of CD146 in HCC has not yet been systematically explored.MethodsTo investigate the role of CD146 in HCC, we evaluated its expression in HCC tissues and HCC cell lines using real-time PCR and western blotting (WB). Second, we established HCC cell lines that stably overexpressed and interfered CD146 and explored the function of CD146 in HCC in vitro and in vivo. Third, we conducted microarray analysis to investigate the potential mechanism by identifying differentially expressed genes. Last, follow ups were conducted to help uncover the connection of CD146 expression and the prognosis of HCC patients.ResultsWe found that CD146 was overexpressed in HCC tissues and that high CD146 expression predicted poor overall survival time and shorter recurrence period in HCC patients. In vitro and in vivo experiments indicated that CD146 promoted migration and invasion of HCC cell lines. Further study indicated that CD146 promoted epithelial mesenchymal transition (EMT), IL-8 upregulation, and STAT1 downregulation. CD146 was upregulated in HCC tissues and cell lines.ConclusionsCD146 promoted metastasis of HCC cells and predicted poor prognosis of HCC patients. CD146 induced EMT, and IL-8 upregulation and STAT1 downregulation may be the potential underlying mechanism. The exact mechanism still needs further investigation.