Objective: To screen the pivotal genes involved in the occurrence and development of HBV-associated HCC. Additionally, perform validation and biological function analysis to evaluate changes in the expression of pivotal genes and their prognostic value in patients with hepatocellular carcinoma. Methods: The GSE121248 gene expression profile data of HBV-HCC patients were searched and downloaded from the GEO database. The R language was used to compare the differences in gene expression between hepatocellular carcinoma and paracancerous tissues. KEGG and GO function enrichment analyses were performed on the differential genes. PPI plots and pivotal gene screening were carried out through online tools like STRING and Cytoscape software. 369 cases of hepatocellular carcinoma and 160 healthy controls in TCGA and GTEx were used as validation cohorts to verify the expression levels of the pivotal genes. A Kaplan-Meier plot was drawn to evaluate the prognostic value of the pivotal gene. Results: A total of 120 differentially expressed genes were screened, of which 89 were up-regulated and 31 were down-regulated. Differential genes were mainly enriched in the metabolic pathways related to retinol metabolism, cytochrome P450 metabolism, and the p53 signaling pathway. The top 10 differential genes were selected as pivotal genes by the Cytoscape plug-in cytoHubba. There were significant differences in the expression levels of four types of CCNB1, CDK1, RRM2, and TOP2A genes in the validation cohort. All four types of genes were up-regulated. Survival analysis showed that patients with elevated expression levels of four genes had a poorer prognosis, with statistical differences in results. Conclusion: Four types of genes, CCNB1, CDK1, RRM2, and TOP2A, have high expression levels in patients with HBV-HCC and are correlated to shorter survival times, making them a potential target for diagnosis, prognosis, and treatment.
目的： 筛选乙型肝炎相关性肝细胞癌发生和发展的枢纽基因，并进行验证和生物学功能分析。以评估枢纽基因在肝细胞癌患者表达量的变化及其预后价值。 方法： 从GEO数据库中搜索并下载乙型肝炎相关性肝细胞癌患者基因表达数据GSE121248，通过R语言比较肝癌组织和癌旁组织基因表达的差异，并对差异基因进行KEGG和GO功能富集分析。通过在线工具STRING和Cytoscape软件绘制PPI和筛选枢纽基因。以TCGA和GTEx中的369例肝细胞癌患者和160名健康对照为验证队列验证枢纽基因的表达量，绘制Kaplan-Meier图评估枢纽基因的预后价值。 结果： 共筛选出差异基因120个，其中89上调个，31下调个。差异基因主要富集于视黄醇代谢、细胞色素P450代谢、p53信号通路相关代谢途径中，通过Cytoscape的CytoHubba插件筛选前10个差异基因为枢纽基因，验证队列中CCNB1、CDK1、RRM2和TOP2A 4种基因表达量具有显著差异，4种基因均为上调基因。生存分析显示4种基因表达量升高的患者预后较差，结果存在统计学差异。 结论： CCNB1、CDK1、RRM2和TOP2A 4种基因在HBV-肝细胞癌患者中表达量升高，并与患者较短生存期相关，是潜在的诊断、预后和治疗的靶标。.
Keywords: Bioinformatics; Hepatitis B; Hepatocellular carcinoma.