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24 May 2018 : Laboratory Research  

Identification of Biological Targets of Therapeutic Intervention for Hepatocellular Carcinoma by Integrated Bioinformatical Analysis

Wei Qi Hu1ABCDEF, Wei Wang1AF, Di Long Fang1BDF, Xue Feng Yin1ACEF

DOI: 10.12659/MSM.909290

Med Sci Monit 2018; 24: LBR3450-3461

Abstract

BACKGROUND: We screened the potential molecular targets and investigated the molecular mechanisms of hepatocellular carcinoma (HCC).

MATERIAL AND METHODS: Microarray data of GSE47786, including the 40 μM berberine-treated HepG2 human hepatoma cell line and 0.08% DMSO-treated as control cells samples, was downloaded from the GEO database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed; the protein–protein interaction (PPI) networks were constructed using STRING database and Cytoscape; the genetic alteration, neighboring genes networks, and survival analysis of hub genes were explored by cBio portal; and the expression of mRNA level of hub genes was obtained from the Oncomine databases.

RESULTS: A total of 56 upregulated and 8 downregulated DEGs were identified. The GO analysis results were significantly enriched in cell-cycle arrest, regulation of transcription, DNA-dependent, protein amino acid phosphorylation, cell cycle, and apoptosis. The KEGG pathway analysis showed that DEGs were enriched in MAPK signaling pathway, ErbB signaling pathway, and p53 signaling pathway. JUN, EGR1, MYC, and CDKN1A were identified as hub genes in PPI networks. The genetic alteration of hub genes was mainly concentrated in amplification. TP53, NDRG1, and MAPK15 were found in neighboring genes networks. Altered genes had worse overall survival and disease-free survival than unaltered genes. The expressions of EGR1, MYC, and CDKN1A were significantly increased, but expression of JUN was not, in the Roessler Liver datasets.

CONCLUSIONS: We found that JUN, EGR1, MYC, and CDKN1A might be used as diagnostic and therapeutic molecular biomarkers and broaden our understanding of the molecular mechanisms of HCC.

Keywords: Berberine

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750