肿瘤组织中 BUB1B、CCNB1、CDC7、CDC20 和 MCM3 的上调预示着肝细胞癌患者总体生存和无病生存更差。

OBJECTIVE: To evaluate the association between upregulated differentially expressed genes (DEGs) and the outcomes of patients with hepatocellular carcinoma (HCC). METHODS: Using Gene Expression Omnibus (GEO) datasets including GSE45436, GSE55092, GSE60502, GSE84402, and GSE17548, we detected upregulated DEGs in tumors. KEGG, GO, and Reactome enrichment analysis of the DEGs was conducted to clarify their function. The impact of the upregulated DEGs on patients' survival was analyzed based on TCGA profile. RESULTS: 161 shared upregulated DEGs were identified among GSE45436, GSE55092, GSE60502, and GSE84402 profiles. Cell cycle was the shared pathway/biological process in the gene sets investigation among databases of KEGG, GO, and Reactome. After being validated in GSE17548, 13 genes including BUB1B, CCNA2, CCNB1, CCNE2, CDC20, CDC6, CDC7, CDK1, CDK4, CDKN2A, CHEK1, MAD2L1, and MCM3 in cell cycle pathway were shared in the three databases for enrichment. The expression of BUB1B, CCNB1, CDC7, CDC20, and MCM3 was upregulated in HCC tissues when compared with adjacent normal tissues in 6.67%, 7.5%, 8.06%, 5.56%, and 9.72% of HCC patients, respectively. Overexpression of BUB1B, CCNB1, CDC7, CDC20, and MCM3 in HCC tissues accounted for poorer overall survival (OS) and disease-free survival (DFS) in HCC patients (all log rank < 0.05). BUB1B, CCNB1, CDC7, CDC20, and MCM3 were all overexpressed in HCC patients with neoplasm histologic grade G3-4 compared to those with G1-2 (all < 0.05). BUB1B, CCNB1, and CDC20 were significantly upregulated in HCC patients with vascular invasion (all < 0.05). Additionally, levels of BUB1B, CCNB1, CDC7, and CDC20 were significantly higher in HCC patients deceased, recurred, or progressed (all < 0.05). CONCLUSION: Correlated with advanced histologic grade and/or vascular invasion, upregulation of BUB1B, CCNB1, CDC7, CDC20, and MCM3 in HCC tissues predicted worse OS and DFS in HCC patients. These genes could be novel therapeutic targets for HCC treatment.

目的：评估上调差异表达基因（DEGs）与肝细胞癌（HCC）患者结局之间的关系。

方法：使用基因表达综合数据库（GEO）数据集，包括 GSE45436、GSE55092、GSE60502、GSE84402 和 GSE17548，我们检测了肿瘤中的上调 DEGs。对 DEGs 进行 KEGG、GO 和 Reactome 富集分析，以阐明其功能。基于 TCGA 图谱分析上调 DEGs 对患者生存的影响。

结果：在 GSE45436、GSE55092、GSE60502 和 GSE84402 图谱中鉴定出 161 个共有上调 DEGs。细胞周期是 KEGG、GO 和 Reactome 基因集研究中的共同途径/生物学过程。在 GSE17548 中验证后，在三个数据库中，细胞周期途径中共有的 13 个基因（BUB1B、CCNA2、CCNB1、CCNE2、CDC20、CDC6、CDC7、CDK1、CDK4、CDKN2A、CHEK1、MAD2L1 和 MCM3）被富集。在 6.67%、7.5%、8.06%、5.56%和 9.72%的 HCC 患者中，与相邻正常组织相比，HCC 组织中 BUB1B、CCNB1、CDC7、CDC20 和 MCM3 的表达上调。在 HCC 患者中，BUB1B、CCNB1、CDC7、CDC20 和 MCM3 的高表达与较差的总生存期（OS）和无病生存期（DFS）相关（均 log rank < 0.05）。与 G1-2 相比，HCC 患者中组织学分级 G3-4 的 BUB1B、CCNB1 和 CDC20 均过度表达（均 < 0.05）。BUB1B、CCNB1 和 CDC20 在伴有血管侵犯的 HCC 患者中显著上调（均 < 0.05）。此外，在 HCC 患者死亡、复发或进展时，BUB1B、CCNB1、CDC7 和 CDC20 的水平显著升高（均 < 0.05）。

结论：与高级组织学分级和/或血管侵犯相关，HCC 组织中 BUB1B、CCNB1、CDC7、CDC20 和 MCM3 的上调预示着 HCC 患者 OS 和 DFS 较差。这些基因可能成为 HCC 治疗的新的治疗靶点。