This study aimed to identify key functional modules and genes in functional module involved in hepatocellular carcinoma (HCC) development. The microarray data set GSE54236 was obtained from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between HCC, and normal samples were identified by Limma. DAVID was used to identify the gene ontology terms these genes enriched. The co-expression network was constructed based on Pearson correlation coefficient between gene expression values, and the functional modules these DEGs obviously enriched in were recognized through GraphWeb. Then, based on the genes related to the development of HCC, the DEGs interacting with HCC-associated genes were spotted. Finally, survival analysis and real-time quantitative polymerase chain reaction were performed. Totally, 427 upregulated (e.g., cell division cycle associated 5 [CDCA5], kinesin family member 4A [KIF4A], TPX2 microtubule nucleation factor [TPX2]) and 313 downregulated (e.g., metallothionein 1E [MT1E]) DEGs were identified in HCC. Besides, CDCA5, KIF4A, and TPX2 had interacting relationship and played important roles in HCC development by interrelating with HCC-related gene, forkhead box M1 (FOXM1). Furthermore, CDCA5, KIF4A, TPX2, and FOXM1 obviously enriched in cell cycle-related functional module, whereas MT1E enriched in mineral absorption module in Kyoto Encyclopedia of Genes and Genomes. CDCA5, KIF4A, and TPX2 expression were increased in HCC cells, and their high expressions were related to poor prognosis. Overexpression of CDCA5, KIF4A, TPX2, and FOXM1 coregulated cell cycle and thereby promoted the development of HCC. The finding provided potential targets for the study and treatment of HCC.
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