Background and Aims: Hepatocellular carcinoma (HCC) is a common primary liver cancer with a poor prognosis. The activation and inactivation of genes can promote the occurrence and development of HCC. This study was conducted to investigate the key genes and their functions in the occurrence and development of HCC based on bioinformatics and verify their expressions in clinical samples. 
Methods: The HCC and paracancerous tissue gene chips were downloaded from the public gene GEO database, the differentially expressed genes (DEGs) were screened through GEO2R online tools and Venn diagrams, and the GO function analysis and KEGG pathway enrichment analysis were performed on the selected DEGs using the DAVID website, and then the core DEGs were picked up from the DEGs by protein-protein interaction (PPI) network analysis using STRING website and Cytscape software. The prognosis-related DEGs were determined by survival analysis using Kaplan-Meier Plotter website, and the expression levels of the prognosis-related DEGs were analyzed using the GEPIA website to obtain the differential expressions betwen HCC and paracancerous tissue, and then the key genes associated with the occurrence and development of HCC were screened from the highly expressed prognosis-related DEGs in HCC by function and enrichment pathway analysis using Metascape website. Finally, the expression verification of select key genes was performed in the specimens of HCC and paracancerous tissue.
Results: A total of 78 DEGs were screened from the three eligible gene chips (GSE14520, GSE41804, GSE45267) downloaded from GEO. Then, 17 core DEGs (CDK1, ASPM,CENPF, RRM2, CCNB1, TOP2A, PTTG1, ECT2, CDKN3, CYP2B6,SLCO1B3, CYP1A2, CYP4A11, CYP26A1,CYP2E1,NAT2, CYP3A4) were screened out after using DAVID website GO function analysis and KEGG pathway enrichment analysis as well as STRING website and Cytscape software analysis. After the survival analysis of the 17 core DEGs on Kaplan-Meier Plotter website, 9 genes (CDK1, ASPM, CENPF, RRM2, CCNB1, TOP2A, PTTG1, ECT2, CDKN3) were detected to be associated with the prognosis of HCC (all P<0.05). The expression level analysis by GEPIA website showed that all the 9 genes were highly expressed in HCC tissue (all P<0.05). Metascape website analysis showed that the 9 highly expressed genes were mainly enriched in the processes of negative regulation of mitotic cell cycle, nuclear chromosome segregation and female gamete generation. The CDK1 was selected to verify in HCC and paracancerous tissues, and the result showed that the CDK1 expression level was significantly higher than that in paracancerous tissue (P<0.05).
Conclusion: The 9 genes obtained in this study may be the key genes in the occurrence and development of HCC, which provide a reference for the study of the pathogenetic mechanism as well as the diagnosis and treatment of HCC.