Identifying hub genes and dysregulated pathways in hepatocellular carcinoma

B. Jin, W. Wang, G. Du, G.-Z. Huang, L.-T. Han, Z.-Y. Tang, D.-G. Fan, J. Li, S.-Z. Zhang

The Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China. binjin1@yeah.net

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• Oncology

OBJECTIVE: The aim of this study was to identify the hub genes and dysregulated pathways of hepatocellular carcinoma (HCC) and explore the molecular mechanism of the biological process associated with HCC.

MATERIALS AND METHODS: Microarray data were got from NCBI Gene Expression Omnibus (GEO) database. The most significant top 100 up-regulated gene signatures and top 100 down-regulated gene signatures were identified by integrated analysis of the multiple microarray datasets using a novel model genome-wide relative significance (GWRS) and genome-wide global significance (GWGS). Gene Ontology (GO) enrichment analysis and pathway analysis of those genes were performed based on Gene Ontology website and Kyoto Encyclopedia of Genes and Genomes (KEGG). Protein-protein interaction (PPI) network was constructed using Cytoscape 2.1. In addition, we analysed the significantly dysregulated signaling pathways across the PPI network and KEGG pathway analysis.

RESULTS: We screened 2920 up-regulated and 2231 down-regulated gene signatures across multiple studies by GWRS and GWGS. The top 100 up-regulated and top 100 down-regulated gene signatures were selected for further research. GO enrichment analysis showed that these genes significantly enriched in terms of mitosis (p = 5.83×10-20), nuclear division (p = 5.83×10-20) and M phase of mitotic cell cycle (p = 9.39×10-20). The most significant terms of KEGG pathway included cell cycle (p = 1.33×10-8), oocyte meiosis (p = 1.41×10-4), drug metabolism (p = 2.15×10-4) and p53 signaling pathway (p = 3.57×10-4). PPI network suggested that BIRC5, CDC20, CCNB1, BUB1B, MAD2L1 and CDK1 were important significant genes which were considered as hub genes. Across the PPI and pathway, cell cycle, oocyte meiosis and p53 signaling pathway were the significantly dysregulated pathways.

CONCLUSIONS: Our study displayed robust gene signatures in HCC. It showed that the dysregulations of cell cycle, oocyte meiosis, p53 signaling pathway and progesterone-mediated oocyte maturation pathway were closely associated to the development and progression of HCC. Besides, genes BIRC5, CDC20, CCNB1, BUB1B, MAD2L1 and CDK1 as the hub genes might play important roles for diagnosing and therapy of HCC.

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