Identification of Potential Hub Genes and Regulatory Network in Hepatoblastoma using Transcriptomic Analysis

Background and Aim: Although hepatoblastoma (HB) is the most common liver cancer in children, it is a rare neoplasm. In addition, patients are usually asymptomatic and are diagnosed at advanced stages of the disease. Therefore, this study aims to investigate molecular mechanisms controlling the tumor behavior using bioinformatic analyses and predict transcription factors (TFs) and hub genes as potential markers for early diagnosis.Methods: We extracted the gene expression profile GSE۱۳۱۳۲۹ from the NCBI Gene Expression Omnibus (GEO) database and identified the differentially expressed genes (DEGs) using the GEO۲R tool (adjPval<۰.۰۵, |fold change|≥۱.۵). To explore the potential TFs associated with HB, TFs among the up-regulated genes were identified using the TFcheckpoint database, followed by the prediction of the TFs controlling these genes using eXpression۲Kinases (X۲K) web. Then, we constructed their protein-protein interaction (PPI) network utilizing the STRING database and visualized it by Cytoscape software. X۲K was also used to establish the inferred upstream regulatory network from the up-regulated genes. Moreover, we produced the PPI network of the up-regulated genes by STRING and then used the Cytohubba plug-in for Cytoscape to screen hub genes from the PPI network. Finally, we performed Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the hub genes by the EnrichR database.Results: In total, our study identified ۵۹۴ DEGs, including ۲۲۱ up-regulated and ۳۷۳ down-regulated genes. The PPI network constructed between the TFs included ۱۷ nodes and ۱۵ edges. FOXM۱ was the only TF overlapping among the two TF groups. Furthermore, the top ten genes ranked by the Degree algorithm were selected as hub genes: CDK۱, CCNB۱, AURKA, CCNA۲, PLK۱, TOP۲A, CDC۲۰, HIST۱H۲BH, PBK, and HIST۱H۲BD. GO analysis revealed that the hub genes were mainly involved in processes associated with cell cycle and ubiquitin-protein ligase activity. Moreover, KEGG pathway analysis showed that the genes were enriched in cell cycle, viral carcinogenesis, cellular senescence, and p۵۳ signaling pathways.Conclusion: The findings of this study can be implemented to better understand the underlying molecular mechanisms regarding the development of HB and provide novel prognostic markers and therapeutic strategies.

کلیدواژه ها:

Hepatoblastoma ، Regulatory network ، Hub genes ، Transcription factor ، Pathway ، Protein-protein interaction network