Comprehensive analysis of partial epithelial mesenchymal transition-related genes in hepatocellular carcinoma.

Comprehensive analysis of partial epithelial mesenchymal transition-related genes in hepatocellular carcinoma.
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肝细胞癌部分上皮间质转化相关基因的综合分析

DOI:
10.1111/jcmm.16099
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发表时间:
2021-01
影响因子:
5.3
通讯作者:
Han P
Han P
中科院分区:
医学2区
文献类型:
--
作者:
Lei Y;Yan W;Lin Z;Liu J;Tian D;Han P

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越来越多的证据表明,处于中间状态的癌细胞,即部分上皮间充质转化(p-EMT),往往会发生转移,而不是完全转移。我们对E-钙粘蛋白和25个p-EMT相关基因在肝细胞癌中的表达进行了综合分析,以探讨它们在肝细胞癌中的作用和调控机制。我们利用生物信息学方法分析了E-钙粘蛋白和25个p-EMT相关基因,构建了包含p-EMT相关基因的mRNA-miRNA-lncRNA Cerna亚网络。免疫组织化学方法检测p-EMT关键相关基因P4HA2、ITGA5、MMP9、MT1X和SPP1的蛋白表达。完整的EMT对于肝细胞癌的进展并不是必需的。肝细胞癌组织中P4HA2、ITGA5、MMP9、SPP1的高表达和MT1X的低表达与患者的预后不良密切相关。通过从mRNA到lncRNA的逐步反向预测和验证,通过表达和生存分析,确定了一个与肝癌预后相关的mRNA-miRNA-lncRNA Cerna亚网络。提示p-EMT相关关键基因P4HA2、ITGA5、MMP9、MT1X、SPP1可作为预测肝癌预后的生物标志物和潜在的治疗靶点。我们成功构建了包含p-EMT相关基因的mRNA-miRNA-lncRNA子网络,其中每一组分都可能作为肝细胞癌预后的生物标志物。
Increasing evidence has revealed that cancer cells undergoing an intermediate state, partial epithelial mesenchymal transition (p‐EMT), tend to metastasize rather than complete EMT. We performed a comprehensive analysis of E‐cadherin and 25 p‐EMT‐related genes in HCC to explore the roles and regulatory mechanisms of them in HCC. We analysed E‐cadherin and 25 p‐EMT‐related genes in HCC and constructed an mRNA‐miRNA‐lncRNA ceRNA subnetwork containing p‐EMT‐related genes by bioinformatic approaches. IHC was used to identify the protein expression of key p‐EMT‐related genes, P4HA2, ITGA5, MMP9, MT1X and SPP1. Complete EMT is not necessary for HCC progression. Overexpression of P4HA2, ITGA5, MMP9, SPP1 and down‐regulation of MT1X were found in HCC tissues, which were significantly associated with poor prognosis of HCC patients. By means of stepwise reverse prediction and validation from mRNA to lncRNA, an mRNA‐miRNA‐lncRNA ceRNA subnetwork correlated with HCC prognosis was identified by expression and survival analysis. This study implied that key p‐EMT‐related genes P4HA2, ITGA5, MMP9, MT1X, SPP1 could be prognostic biomarkers and potential targets of therapy for HCC patients. We constructed an mRNA‐miRNA‐lncRNA subnetwork containing p‐EMT‐related genes successfully, among which each component might be utilized as a prognostic biomarker of HCC.
DOI: 10.1002/hep.27492
发表时间: 2015-03
期刊: HEPATOLOGY
影响因子: 13.5
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