Up-Regulation of hsa-miR-210 Promotes Venous Metastasis and Predicts Poor Prognosis in Hepatocellular Carcinoma
Up-Regulation of hsa-miR-210 Promotes Venous Metastasis and Predicts Poor Prognosis in Hepatocellular Carcinoma
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DOI：
10.3389/fonc.2018.00569
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发表时间：
2018-12-03
影响因子：
4.7
通讯作者：
Wang, Fu-Bing
中科院分区：
文献类型：
--
作者：
Ji, Jia;Rong, Yuan;Wang, Fu-Bing
目的：目的：探讨肝细胞癌静脉转移的潜在生物标志物，并简要讨论其靶基因及其参与的信号通路。材料与方法：数据集GSE 6857从GEO下载。采用R软件包“limma”对差异表达的miRNAs进行鉴定，并进行生存分析，探讨这些上调的miRNAs对HCC患者预后的意义。此外，在静脉转移阳性的HCC组织中上调并对HCC患者的预后具有重要意义的miRNAs在临床样本中使用RT-qPCR进一步验证。然后使用从TOGA数据库下载的375个HCC样本分析miRNAs与临床特征的相关性，包括生存时间、AFP水平、病理分级、TNM分期、肿瘤分期、淋巴结转移、远处转移、child-pugh评分、血管浸润、肝纤维化和种族。结果：15条miRNA在肝癌静脉转移组织中差异表达，其中7条在静脉转移阳性肝癌组织中表达上调。hsa-miR-210作为上调的miRNAs之一，被认为是HCC的独立预后因子。使用RT-qPCR，明显的是，hsa-miR-210表达在静脉转移阳性HCC样品中显著更高（p = 0.0036）。进一步分析发现hsa-miR-210与AFP水平、病理分级、TNM分期、肿瘤分期和血管浸润呈正相关。结论：hsa-miR-210可能促进肝癌细胞的血管侵袭，可作为肝癌预后的生物标志物。
Objective: To investigate the potential biomarkers for venous metastasis of hepatocellular carcinoma (HCC), and briefly discuss their target genes and the signaling pathways they are involved in.Materials and Method: The dataset GSE6857 was downloaded from GEO. Significantly differentially expressed miRNAs were identified using the R package "limma," After that, the survival analysis was conducted to discover the significance of these up-regulated miRNAs for the prognosis of HCC patients. Additionally, miRNAs which were up-regulated in venous metastasis positive HCC tissues and were significant for the prognosis of HCC patients were further verified in clinical samples using RT-qPCR. The miRNAs were then analyzed for their correlations with clinical characteristics including survival time, AFP level, pathological grade, TNM stage, tumor stage, lymph-node metastasis, distant metastasis, child-pugh score, vascular invasion, liver fibrosis and race using 375 HCC samples downloaded from the TOGA database. The target genes of these miRNAs were obtained using a miRNA target gene prediction database, and their functions were analyzed using the online tool DAVID.Results: 15 miRNAs were differentially expressed in samples with venous metastasis, among which 7 were up-regulated in venous metastasis positive HCC samples. As one of the up-regulated miRNAs, hsa-miR-210 was identified as an independent prognostic factor for HCC. Using RT-qPCR, it was evident that hsa-miR-210 expression was significantly higher in venous metastasis positive HCC samples (p = 0.0036). Further analysis indicated that hsa-miR-210 was positively associated with AFP level, pathological grade, TNM stage, tumor stage and vascular invasion. A total of 168 hsa-miR-210 target genes, which are mainly related to tumor metastasis and tumor signaling pathways, were also predicted in this study.Conclusion: hsa-miR-210 might promote vascular invasion of HCC cells and could be used as a prognostic biomarker.