Identification and Analysis of the Key Genes associated with the Development from Liver Cirrhosis to Hepatocellular Carcinoma Based on Bioinformatics Analysis

Abstract

Background: Hepatocellular carcinoma (HCC) is the most frequent primary liver tumor, and one of the most common malignant cancer with poor prognosis. Liver cirrhosis is the major risk factor for HCC. The aim of this study was to identify potential key genes associated with the development from liver cirrhosis to HCC and explore their potential mechanisms. Methods: Four microarray datasets GSE17548, GSE63898, GSE25097 and GSE89377 were downloaded from the Gene Expression Omnibus database. A protein-protein interaction (PPI) network was constructed using the STRING database, and potential hub genes were screened using MCODE plug-in in Cytoscape software. The Oncomine database was used to verify the expression of differential genes in cirrhosis and HCC. In order to further verify those hub genes, the hierarchical cluster between normal and HCC tissues was constructed using the UCSC Cancer Genomics Browser. The UALCAN database was used to verify the difference of hub genes in normal and HCC tissues and in different tumor grades. Finally, the cBioPortal online platform was used to analyze the association between the expression of hub genes and prognosis in HCC.Results: A total of 360 DEGs, including 280 downregulated and 80 upregulated genes, were identified. Gene ontology enrichment (GO) analysis showed that these DEGs were mainly enriched in monooxygenase activity, cofactor binding, and oxidoreductase activity (acting on CH-OH group of donors). The mainly enriched pathways were complement and coagulation cascades, prion diseases, and arachidonic acid metabolism. By extracting key modules from the PPI network, 16 hub genes were screened out. In the hierarchical cluster of hub genes between normal and HCC tissues, the results showed that the expression level of 16 hub genes in HCC tissues was significantly higher than that in normal tissues. In addition, expression level of the hub genes was significantly associated with the tumor grades. The survival analysis showed that six hub DEGs, including KIF20A,HMMR, RRM2, TPX2, TTK and UBE2C, were closely associated with the poor prognosis of HCC.Conclusion: Our study discovered six novel potential genes associated with the development from liver cirrhosis to HCC. These key genes may be used as prognostic biomarkers and molecular therapeutic targets for HCC.