摘要
慢性乙型肝炎病毒(Hepatitis B virus,HBV)感染引起的原发性肝癌涉及多种基因、转录本和蛋白质的相互作用及调控。从单个基因的角度来看,某个基因的表达量的改变只能对肝癌发生发展的局部作出解释而无法从整体行为进行深入和全面的探索,无法满足高度复杂性的调控研究需要。筛选乙肝相关性肝癌的基因芯片数据获取差异表达基因后,应用加权基因共表达网络分析算法构建基因共表达网络,识别与肝癌发生相关的模块,利用可视化筛选枢纽基因,并针对枢纽基因进行基因本体富集分析和初步验证。富集分析和文献挖掘一致发现,某些枢纽基因确实与多种癌症的发生与发展存在显著的关联。权重基因共表达网络分析方法被证明是一个高效的系统生物学方法,应用该方法发现了新的HBV相关性肝癌枢纽基因。经实验验证,发现枢纽基因SHARPIN促进细胞迁移。该研究对肝癌发生的调控机制以及发现HBV慢性感染导致肝癌的新型诊断标志物和(或)药物作用靶点提供了新的视野。
Primary hepatocellular carcinoma( HCC) caused by chronic hepatitis B virus( HBV) infection involves in a variety of genes,transcripts,proteins and their interactions and regulations with each other. From the perspective of a single gene,the alteration of its expression profile only explains the local occurrence of liver cancer but not in the overall and comprehensive understanding,which is unable to meet needs of the highly complicated disease network studies. Differentially expressed genes screened from the gene chip data of HBV-related HCC were analyzed by the weighted gene co-expression network analysis( WGCNA) algorithm to construct the co-expression gene network and identify the HCC-related modules. In this paper,hub genes were visually screened and determined via the gene ontology enrichment analysis with the preliminary identification. Given to the function analysis and the literature surveys,we consistently found that indeed there is a significant association between some genes and the pathogenesis of multiple cancers. WGCNA,approach of system biology,was applied to screen the hub genes for HBV-related HCC and approved to be efficient. SHARPIN,one of the screened hub genes,was found to promote cell migration. The present study has given the novel insight into the understanding of the regulatory mechanism during the progression of liver cancer and the discovery of new diagnosis biomarkers as well as antiviral targets.
出处
《生物信息学》
2016年第4期203-212,共10页
Chinese Journal of Bioinformatics
基金
湖北省自然科学基金重点项目(No.2014CFA075)
武汉市科技局应用基础研究项目(No.2015060101010033)
