Differential combinatorial regulatory network analysis related to venous metastasis of hepatocellular carcinoma.
Differential combinatorial regulatory network analysis related to venous metastasis of hepatocellular carcinoma.
复制标题
肝细胞癌静脉转移相关的差异组合调控网络分析。
DOI：
10.1186/1471-2164-13-s8-s14
复制
发表时间：
2012
期刊：
影响因子：
4.4
通讯作者：
Xie L
中科院分区：
文献类型：
--
作者：
Zeng L;Yu J;Huang T;Jia H;Dong Q;He F;Yuan W;Qin L;Li Y;Xie L
肝细胞癌是世界上最致命的癌症之一，而肝细胞癌的转移是导致其高死亡率的重要原因。然而，肝细胞癌转移背后的分子机制尚不完全清楚。对调控网络的研究有助于从系统生物学的角度研究肝细胞癌的转移。利用序列信息和同一队列中无静脉或有静脉转移的肝细胞癌患者的平行microRNA(MiRNA)和mRNA表达数据，我们构建了包含转录因子(Tf)调控和miRNA调控的无转移和转移肝癌的组合调控网络。通过比较非转移和转移网络，分析不同的调控模式、分类的标记模块和关键的调控miRNAs。在全球范围内，信托基金占监管的主要部分，而miRNAs占监管的次要部分。然而，miRNAs在转移性网络中的作用比在非转移性网络中更活跃。17个区分转移状态的差异调控模块被确定为累积模块分类器，该模块也可以区分生存时间。MiR-16、miR-30a、let-7e和miR-204被认为是促进肝癌转移的关键miRNA调控因子。在这项工作中，我们展示了一种综合的方法来进行不同的组合调控网络分析，在特定的背景下，乙肝肝细胞癌的静脉转移。我们的结果提出了不同的肝细胞癌转移亚群背后可能的转录调控模式。这项研究的工作流程可以应用于类似的癌症研究背景，也可以扩展到其他临床课题。
Hepatocellular carcinoma (HCC) is one of the most fatal cancers in the world, and metastasis is a significant cause to the high mortality in patients with HCC. However, the molecular mechanism behind HCC metastasis is not fully understood. Study of regulatory networks may help investigate HCC metastasis in the way of systems biology profiling. By utilizing both sequence information and parallel microRNA(miRNA) and mRNA expression data on the same cohort of HBV related HCC patients without or with venous metastasis, we constructed combinatorial regulatory networks of non-metastatic and metastatic HCC which contain transcription factor(TF) regulation and miRNA regulation. Differential regulation patterns, classifying marker modules, and key regulatory miRNAs were analyzed by comparing non-metastatic and metastatic networks. Globally TFs accounted for the main part of regulation while miRNAs for the minor part of regulation. However miRNAs displayed a more active role in the metastatic network than in the non-metastatic one. Seventeen differential regulatory modules discriminative of the metastatic status were identified as cumulative-module classifier, which could also distinguish survival time. MiR-16, miR-30a, Let-7e and miR-204 were identified as key miRNA regulators contributed to HCC metastasis. In this work we demonstrated an integrative approach to conduct differential combinatorial regulatory network analysis in the specific context venous metastasis of HBV-HCC. Our results proposed possible transcriptional regulatory patterns underlying the different metastatic subgroups of HCC. The workflow in this study can be applied in similar context of cancer research and could also be extended to other clinical topics.