Functional and topological properties in hepatocellular carcinoma transcriptome.
Functional and topological properties in hepatocellular carcinoma transcriptome.
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DOI：
10.1371/journal.pone.0035510
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Malfertheiner P
中科院分区：
文献类型：
--
作者：
Drozdov I;Bornschein J;Wex T;Valeyev NV;Tsoka S;Malfertheiner P
肝细胞癌是全球癌症死亡的主要原因。然而，对肿瘤形成和发病机制的确切分子机制知之甚少。这项研究的主要目标是通过探索高质量的微阵列数据来阐明全基因组分子网络与多种病因的肝细胞癌的发展有关。我们对264个人类基因芯片图谱进行了比较网络分析，监测了健康肝脏、肝硬变和由病毒和酒精引起的肝细胞癌的转录变化。通过基因共表达谱分析，建立了一个由798个基因和2,012个链接组成的共同的肝细胞癌进展相关基因网络。进一步证实肝细胞癌相互作用组具表型特异性和非随机性。此外，我们证实，共表达的基因更有可能共享生物学功能，但不是亚细胞定位。对单个肝癌基因的分析表明，它们在人类蛋白质-蛋白质相互作用网络中处于拓扑中心。我们在一组正常肝组织(n = 8)、丙型肝炎病毒诱导的慢性肝病(n = 9)和肝细胞癌(n = 7)中使用定量RT-PCR来验证几个连接良好的基因的共表达，即ASPM、CDKN3、NEK2、RACGAP1和TOP2A。我们发现，肝细胞癌是一种异质性疾病，其基础是免疫反应、细胞周期和信使核糖核酸翻译通路之间复杂的串扰。我们的工作为更深入地了解肝细胞癌进展的分子机制提供了系统范围的资源，并可能被进一步用于定义有效治疗或诊断这种疾病的新靶点。
Hepatocellular carcinoma (HCC) is a leading cause of global cancer mortality. However, little is known about the precise molecular mechanisms involved in tumor formation and pathogenesis. The primary goal of this study was to elucidate genome-wide molecular networks involved in development of HCC with multiple etiologies by exploring high quality microarray data. We undertook a comparative network analysis across 264 human microarray profiles monitoring transcript changes in healthy liver, liver cirrhosis, and HCC with viral and alcoholic etiologies. Gene co-expression profiling was used to derive a consensus gene relevance network of HCC progression that consisted of 798 genes and 2,012 links. The HCC interactome was further confirmed to be phenotype-specific and non-random. Additionally, we confirmed that co-expressed genes are more likely to share biological function, but not sub-cellular localization. Analysis of individual HCC genes revealed that they are topologically central in a human protein-protein interaction network. We used quantitative RT-PCR in a cohort of normal liver tissue (n = 8), hepatitis C virus (HCV)-induced chronic liver disease (n = 9), and HCC (n = 7) to validate co-expressions of several well-connected genes, namely ASPM, CDKN3, NEK2, RACGAP1, and TOP2A. We show that HCC is a heterogeneous disorder, underpinned by complex cross talk between immune response, cell cycle, and mRNA translation pathways. Our work provides a systems-wide resource for deeper understanding of molecular mechanisms in HCC progression and may be used further to define novel targets for efficient treatment or diagnosis of this disease.
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影响因子：
3.7
作者：
Barrenas F;Chavali S;Holme P;Mobini R;Benson M
通讯作者：
Benson M
影响因子：
4.3
作者：
Bae, I;Rih, JK;Rosen, EM
通讯作者：
Rosen, EM
影响因子：
6.2
作者：
Braconi, Chiara;Meng, Fanyin;Patel, Tushar
通讯作者：
Patel, Tushar
影响因子：
8
作者：
Durkin, M. E.;Ullmannova, V.;Popescu, N. C.
通讯作者：
Popescu, N. C.
DOI：
10.1088/1742-5468/2008/10/p10008
发表时间：
2008-10-01
影响因子：
2.4
作者：
Blondel, Vincent D.;Guillaume, Jean-Loup;Lefebvre, Etienne
通讯作者：
Lefebvre, Etienne