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.
Highlights
Hepatocellular carcinoma (HCC) is the most frequent primary liver malignancy and a major cause of cancer-related death worldwide, especially in developing countries [1]
The results showed that ACACB, IGF1, and EHHADH were significantly down-regulated in HCC, and CDK1, CCNB1, CCNB2, MAD2L1, and TOP2A were significantly up-regulated in HCC, which was consistent with the microarray results (Figure 5)
We explored the crucial genes and pathway associated with HCC by bioinformatics methods
Summary
Hepatocellular carcinoma (HCC) is the most frequent primary liver malignancy and a major cause of cancer-related death worldwide, especially in developing countries [1]. A further investigation into the underlying mechanisms of HCC initiation and progression is urgently needed, which will contribute to the discovery of novel diagnostic and therapeutic targets for HCC. There have been many reports of genes and pathways involved in HCC initiation and progression [5,6,7,8]. Zhao et al [6] found c 2018 The Author(s).
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