基于基因表达谱分析的乙肝阳性转移性肝细胞癌的分子机制分析

发布时间：2018-04-17 21:13

本文选题：转移性肝细胞癌 + 差异基因表达　；参考：《基因组学与应用生物学》2017年04期

【摘要】：本研究旨在筛选与乙肝阳性转移性肝细胞癌相关的基因并揭示其潜在的分子机制。利用GEO数据库中GSE364数据集,筛选在肝内扩散转移组和门静脉癌栓转移组都差异表达的基因,DAVID对差异表达基因进行GO与信号通路富集分析,并用STRING和Cytoscape构建蛋白互作网络,随后用mi Rwalk 2.0筛选可能参与肝细胞癌转移的miRNAs,构建miRNA-枢纽基因调控网络。之后使用Smoami R DB 2.0和c Bio Portal分析枢纽基因突变与circRNA和肝细胞癌预后的关系。我们获得在肝内扩散转移组和门静脉癌栓转移组都差异表达的基因701个,富集分析发现这些基因主要涉及血管生成和血管内皮生长因子信号转导等信号通路。从构建的蛋白互作网络中获得参与蛋白互作模式1的15个枢纽基因,GO分析发现其主要参与RNA加工、代谢、剪接等生物过程。构建的miRNA-枢纽基因调控网络中有4个miRNA参与两个枢纽基因的调控,此外肝细胞癌中SRSF1基因有突变并可转录为hsa_circ_0044757,SNRNP200基因突变与患者预后相关。本研究发现的差异表达基因和枢纽基因,有助于我们认识乙肝相关性肝细胞癌转移的分子机制,并可作为新的用于诊断和预后判断的分子标志物。
[Abstract]:The aim of this study was to screen genes associated with hepatitis B positive metastatic hepatocellular carcinoma (HCC) and to reveal its potential molecular mechanism.Using the GSE364 data set in GEO database, the differential expression genes were screened in both intrahepatic diffusive metastasis group and portal vein tumor thrombus metastasis group. The differentially expressed genes were enriched by go and signal pathway, and protein interaction network was constructed by STRING and Cytoscape.Then the miRNA-hinge gene regulatory network was constructed by using mi Rwalk 2.0 to screen the miRNA-pivot gene regulatory network that might be involved in the metastasis of hepatocellular carcinoma.Smoami R DB 2.0 and c Bio Portal were used to analyze the relationship between gene mutation and prognosis of circRNA and hepatocellular carcinoma.We obtained 701 differentially expressed genes in intrahepatic diffusion metastasis group and portal vein tumor thrombus metastasis group. Enrichment analysis revealed that these genes were mainly involved in signal pathways such as angiogenesis and vascular endothelial growth factor signal transduction.Fifteen pivotal genes involved in protein interaction mode 1 were obtained from the constructed protein interaction network. It was found that these genes were mainly involved in biological processes such as RNA processing, metabolism, splicing and so on.In the constructed miRNA-hinge gene regulatory network, four miRNA were involved in the regulation of two pivotal genes. In addition, the mutation of SRSF1 gene in hepatocellular carcinoma was related to the prognosis of patients.The differentially expressed genes and pivot genes found in this study are helpful for us to understand the molecular mechanism of Hepatitis B related hepatocellular carcinoma metastasis and can be used as new molecular markers for diagnosis and prognosis judgment.
【作者单位】：桂林医学院生物化学与分子生物学教研室;
【基金】：国家自然科学基金地区基金(31660317) 广西壮族自治区教育厅科学技术研究项目(YB2014269)共同资助
【分类号】：R512.62;R735.7

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