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. 2020 Feb 7;17(3):1053.
doi: 10.3390/ijerph17031053.

Identification of Potentially Therapeutic Target Genes of Hepatocellular Carcinoma

Chengzhang Li  1 , Jiucheng Xu  1   2
Affiliations

Identification of Potentially Therapeutic Target Genes of Hepatocellular Carcinoma

Chengzhang Li et al. Int J Environ Res Public Health. .

Abstract

Background: Hepatocellular carcinoma (HCC) is a major threat to public health. However, few effective therapeutic strategies exist. We aimed to identify potentially therapeutic target genes of HCC by analyzing three gene expression profiles.

Methods: The gene expression profiles were analyzed with GEO2R, an interactive web tool for gene differential expression analysis, to identify common differentially expressed genes (DEGs). Functional enrichment analyses were then conducted followed by a protein-protein interaction (PPI) network construction with the common DEGs. The PPI network was employed to identify hub genes, and the expression level of the hub genes was validated via data mining the Oncomine database. Survival analysis was carried out to assess the prognosis of hub genes in HCC patients.

Results: A total of 51 common up-regulated DEGs and 201 down-regulated DEGs were obtained after gene differential expression analysis of the profiles. Functional enrichment analyses indicated that these common DEGs are linked to a series of cancer events. We finally identified 10 hub genes, six of which (OIP5, ASPM, NUSAP1, UBE2C, CCNA2, and KIF20A) are reported as novel HCC hub genes. Data mining the Oncomine database validated that the hub genes have a significant high level of expression in HCC samples compared normal samples (t-test, p < 0.05). Survival analysis indicated that overexpression of the hub genes is associated with a significant reduction (p < 0.05) in survival time in HCC patients.

Conclusions: We identified six novel HCC hub genes that might be therapeutic targets for the development of drugs for some HCC patients.

Keywords: MCC algorithm; PPI network; gene expression profile; hepatocellular carcinoma; hub gene.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Venn diagram of common differentially expressed genes (DEGs) from integral analysis of three independent gene expression profiles: (a) up-regulated genes and (b) down-regulated genes from differential expression analysis of three gene expression profiles.
Figure 2
Figure 2
The significantly enriched Gene Ontology (GO) terms and Kyoto Encyclopedia Genes and Genomes (KEGG) pathways of hepatocellular carcinoma (HCC) differentially expressed genes. (a) GO biological process, (b) GO cellular component, and (c) GO molecular function enrichment analysis results of DEGs. (d) GO KEGG pathway enrichment analysis of DEGs in HCC.
Figure 3
Figure 3
The protein-protein interaction network of the hub genes and the DEGs that directly interact with them. Each node represents a gene and each edge represents a direct interaction between two genes. The nodes filled with red in the center represent hub genes; the nodes filled with white represent the genes that interact directly with hub genes.
Figure 4
Figure 4
Validation of HCC hub gene expression levels with data mining of the Oncomine database: (a–j) The gene expression level of the hub genes between HCC tissues and normal liver tissues. *, a significant statistical difference was observed between HCC and normal liver tissues. Based on the analysis of the GSE6764 dataset, ASPM, CCNA2, CDC20, CDCA5, KIF20A, and OIP5 have significantly higher levels of expression in HCC samples compared to normal liver tissues (Student’s t-test, p < 0.05). Similarly, NUSAP1, PRC1, TOP2A, and UBE2C have significantly higher levels of expression in HCC samples compared to normal liver tissues (Student’s t-test, p < 0.05) via analysis of GSE14520 dataset with the Oncomine database (Student’s t-test, p < 0.05).
Figure 5
Figure 5
Kaplan–Meier survival analyses of the HCC hub genes. (a–j) Overexpression of these HCC hub genes is associated with a significant reduction in overall survival time in HCC patients.
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