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.

中文翻译：

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CDCA5、KIF4A、TPX2 和 FOXM1 的过表达协同调节细胞周期并促进肝细胞癌的发展。

本研究旨在确定参与肝细胞癌（HCC）发展的关键功能模块和功能模块中的基因。微阵列数据集 GSE54236 来自基因表达综合 (GEO) 数据库。Limma 鉴定了 HCC 和正常样本之间的差异表达基因 (DEG)。DAVID 用于识别这些基因丰富的基因本体术语。基于基因表达值之间的Pearson相关系数构建共表达网络，通过GraphWeb识别这些DEG明显富集的功能模块。然后，基于与 HCC 发展相关的基因，发现了与 HCC 相关基因相互作用的 DEG。最后，进行生存分析和实时定量聚合酶链反应。总共有 427 个上调（例如，在 HCC 中鉴定了CDCA5、驱动蛋白家族成员4A [ KIF4A ]、TPX2 微管成核因子[ TPX2 ]）和下调的313（例如，金属硫蛋白1E [ MT1E ]）DEG。此外，CDCA5、KIF4A和TPX2与HCC相关基因forkhead box M1（FOXM1）相互关联，在HCC发生发展中发挥重要作用。此外，CDCA5、KIF4A、TPX2和FOXM1明显富含细胞周期相关的功能模块，而MT1E富含京都基因和基因组百科全书矿物质吸收模块。CDCA5、KIF4A和TPX2在HCC细胞中表达增加，其高表达与预后不良有关。CDCA5、KIF4A、TPX2和FOXM1的过表达共同调节细胞周期，从而促进HCC的发展。这一发现为 HCC 的研究和治疗提供了潜在的靶点。