This article is part of the supplement: The International Conference on Intelligent Biology and Medicine (ICIBM) – Genomics

Open Access Research

Differential combinatorial regulatory network analysis related to venous metastasis of hepatocellular carcinoma

Lingyao Zeng12, Jian Yu2, Tao Huang23, Huliang Jia4, Qiongzhu Dong4, Fei He2, Weilan Yuan1, Lunxiu Qin4*, Yixue Li23* and Lu Xie2*

Author affiliations

1 School of Life Science and Technology, Tongji University, Shanghai 200092, P.R.China

2 Shanghai Center for Bioinformation Technology, Shanghai 200235, P.R.China

3 Key Lab of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R.China

4 Liver Cancer Institute and Zhongshan Hospital, Institutes of Biomedical Science, Fudan University, Shanghai 200032, P.R.China

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Citation and License

BMC Genomics 2012, 13(Suppl 8):S14  doi:10.1186/1471-2164-13-S8-S14

Published: 17 December 2012



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.