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. 2018 Nov 9;38(6):BSR20181441.
doi: 10.1042/BSR20181441. Print 2018 Dec 21.

Bioinformatics identification of crucial genes and pathways associated with hepatocellular carcinoma

Xueren Gao  1 , Xixi Wang  2 , Shulong Zhang  3
Affiliations

Bioinformatics identification of crucial genes and pathways associated with hepatocellular carcinoma

Xueren Gao et al. Biosci Rep. .

Abstract

Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide. Up to date, HCC pathogenesis has not been fully understood. The aim of the present study was to identify crucial genes and pathways associated with HCC by bioinformatics methods. The differentially expressed genes (DEGs) between 14 HCC tissues and corresponding non-cancerous tissues were identified using limma package. Gene Ontology (GO) and KEGG pathway enrichment analysis of DEGs were performed by clusterProfiler package. The protein-protein interaction (PPI) network of DEGs was constructed and visualized by STRING database and Cytoscape software, respectively. The crucial genes in PPI network were identified using a Cytoscape plugin, CytoNCA. Furthermore, the effect of the expression level of the crucial genes on HCC patient survival was analyzed by an interactive web-portal, UALCAN. A total of 870 DEGs including 237 up-regulated and 633 down-regulated genes were identified in HCC tissues. KEGG pathway analysis revealed that DEGs were mainly enriched in complement and coagulation cascades pathway, chemical carcinogenesis pathway, retinol metabolism pathway, fatty acid degradation pathway, and valine, leucine and isoleucine degradation pathway. PPI network analysis showed that CDK1, CCNB1, CCNB2, MAD2L1, ACACB, IGF1, TOP2A, and EHHADH were crucial genes. Survival analysis suggested that the high expression of CDK1, CCNB1, CCNB2, MAD2L1, and TOP2A significantly decreased the survival probability of HCC patients. In conclusion, the identification of the above crucial genes and pathways will not only contribute to elucidating the pathogenesis of HCC, but also provide prognostic markers and therapeutic targets for HCC.

Keywords: Crucial gene; Pathway; Survival analysis; hepatocellular carcinoma.

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Conflict of interest statement

The authors declare that there are no competing interests associated with the manuscript.

Figures

Figure 1
Figure 1. Volcano plot of microarray data (upper-left and upper-right blue dots stand for down- and up-regulated genes in HCC, respectively
Figure 2
Figure 2. The top 5 GO terms enriched by DEGs (A, biological process; B, cellular component; C, molecule function)
Figure 3
Figure 3. The top 5 KEGG pathways enriched by DEGs
Figure 4
Figure 4. PPI network plot of DEGs (red and blue nodes stand for up- and down- regulated genes in HCC, respectively)
Figure 5
Figure 5. Boxplots showing the expression level of crucial genes in normal and HCC samples
Figure 6
Figure 6. Kaplan–Meier plots showing the association of the expression level of crucial genes with HCC patient survival
See this image and copyright information in PMC

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