Open Access

Identification of key pathways and biomarkers in sorafenib‑resistant hepatocellular carcinoma using bioinformatics analysis

  • Authors:
    • Danping Huang
    • Weiqu Yuan
    • Hanmin Li
    • Shaodong Li
    • Zuanguang Chen
    • Hongzhi Yang
  • View Affiliations

  • Published online on: July 9, 2018     https://doi.org/10.3892/etm.2018.6427
  • Pages: 1850-1858
  • Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignant types of cancer, with a high mortality rate. Sorafenib is the sole approved oral clinical therapy against advanced HCC. However, individual patients exhibit varying responses to sorafenib and the development of sorafenib resistance has been a new challenge for its clinical efficacy. The current study identified gene biomarkers and key pathways in sorafenib‑resistant HCC using bioinformatics analysis. Gene dataset GSE73571 was obtained from the Gene Expression Omnibus (GEO) database, including four sorafenib‑acquired resistant and three sorafenib‑sensitive HCC phenotypes. Differentially expressed genes (DEGs) were identified using the web tool GEO2R. Functional and pathway enrichment of DEGs were analyzed using the Database for Annotation, Visualization and Integrated Discovery and the protein‑protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins and Cytoscape. A total of 1,319 DEGs were selected, which included 593 upregulated and 726 downregulated genes. Functional and pathway enrichment analysis revealed DEGs enriched in negative regulation of endopeptidase activity, cholesterol homeostasis, DNA replication and repair, coagulation cascades, insulin resistance, RNA transport, cell cycle and others. Eight hub genes, including kininogen 1, vascular cell adhesion molecule 1, apolipoprotein C3, alpha 2‑HS glycoprotein, erb‑b2 receptor tyrosine kinase 2, secreted protein acidic and cysteine rich, vitronectin and vimentin were identified from the PPI network. In conclusion, the present study identified DEGs and key genes in sorafenib‑resistant HCC, which further the knowledge of potential mechanisms in the development of sorafenib resistance and may provide potential targets for early diagnosis and new treatments for sorafenib‑resistant HCC.
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September-2018
Volume 16 Issue 3

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Copy and paste a formatted citation
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Spandidos Publications style
Huang D, Yuan W, Li H, Li S, Chen Z and Yang H: Identification of key pathways and biomarkers in sorafenib‑resistant hepatocellular carcinoma using bioinformatics analysis. Exp Ther Med 16: 1850-1858, 2018
APA
Huang, D., Yuan, W., Li, H., Li, S., Chen, Z., & Yang, H. (2018). Identification of key pathways and biomarkers in sorafenib‑resistant hepatocellular carcinoma using bioinformatics analysis. Experimental and Therapeutic Medicine, 16, 1850-1858. https://doi.org/10.3892/etm.2018.6427
MLA
Huang, D., Yuan, W., Li, H., Li, S., Chen, Z., Yang, H."Identification of key pathways and biomarkers in sorafenib‑resistant hepatocellular carcinoma using bioinformatics analysis". Experimental and Therapeutic Medicine 16.3 (2018): 1850-1858.
Chicago
Huang, D., Yuan, W., Li, H., Li, S., Chen, Z., Yang, H."Identification of key pathways and biomarkers in sorafenib‑resistant hepatocellular carcinoma using bioinformatics analysis". Experimental and Therapeutic Medicine 16, no. 3 (2018): 1850-1858. https://doi.org/10.3892/etm.2018.6427