A comprehensive analysis of the dynamic biological networks in HCV induced hepatocarcinogenesis.
A comprehensive analysis of the dynamic biological networks in HCV induced hepatocarcinogenesis.
复制标题
HCV诱发肝癌动态生物网络的综合分析。
DOI：
10.1371/journal.pone.0018516
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发表时间：
2011-04-19
期刊：
影响因子：
3.7
通讯作者：
Shi T
中科院分区：
文献类型：
--
作者：
He B;Zhang H;Shi T
肝细胞癌（hepatocellular carcinoma，HCC）是一种原发性肝脏恶性肿瘤，与丙型肝炎、肝硬化关系密切。从系统生物学的观点来看，HCV感染诱导肝癌发生的分子机制仍有待阐明。本研究通过整合蛋白质相互作用、转录调控和疾病相关基因芯片分析的数据，对HCV诱发肝癌的过程进行了动态生物网络分析，并从网络的角度系统地探讨了HCV诱发肝癌的潜在机制。蛋白质间相互作用的失调以及转录因子与靶基因间的失调关系可能是导致该病发生和发展的原因。本研究包括HCV感染后HCC发生和进展的六个病理学定义的疾病阶段。我们为每个疾病阶段构建了疾病相关的生物网络，并确定了可能在相应疾病的发展阶段发挥作用并参与癌症进展后期的进展相关子网络。此外，我们根据进展相关子网络的分析确定了与HCC相关的新风险因素。该网络的动态特征反映了疾病发生、发展的重要特征，为我们进一步探讨疾病的潜在机制提供了重要信息。
Hepatocellular carcinoma (HCC) is a primary malignancy of the liver, which is closely related to hepatitis C and cirrhosis. The molecular mechanisms underlying the hepatocarcinogenesis induced by HCV infection remain clarified from a standpoint of systems biology. By integrating data from protein-protein interactions, transcriptional regulation, and disease related microarray analysis, we carried out a dynamic biological network analysis on the progression of HCV induced hepatocarcinogenesis, and systematically explored the potentially disease-related mechanisms through a network view. The dysfunctional interactions among proteins and deregulatory relationships between transcription factors and their target genes could be causes for the occurrence and progression of this disease. The six pathologically defined disease stages in the development and progression of HCC after HCV infection were included in this study. We constructed disease-related biological networks for each disease stage, and identified progression-related sub-networks that potentially play roles in the developmental stage of the corresponding disease and participate in the later stage of cancer progression. In addition, we identified novel risk factors related to HCC based on the analysis of the progression-related sub-networks. The dynamic characteristics of the network reflect important features of the disease development and progression, which provide important information for us to further explore underlying mechanisms of the disease.
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影响因子：
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作者：
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通讯作者：
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