Zhang Zhilan, Zhou Jie, Huang Ruiru, Zhuang Xingxing, Ni Shoudong
College of Pharmacy, Anhui Medical University, Hefei, 230000, Anhui, China.
Department of Pharmacy, Chaohu Hospital of Anhui Medical University, Chaohu, 238000, Anhui, China.
Discov Oncol. 2025 Mar 24;16(1):384. doi: 10.1007/s12672-025-02182-2.
Hepatocellular carcinoma (HCC), originating in the liver and often asymptomatic in early stages, frequently metastasises and recures post-surgery. Currently, reliable diagnostic biomarkers and therapeutic targets for HCC are lacking. This study investigates the influence of cellular senescence on HCC, employing bioinformatics analysis and in vitro experiments to identify potential biomarkers.
We integrated data from GEO microarrays (GSE14520, GSE45267 and GSE64041) to analyse differentially expressed genes (DEGs) using the R package limma. WGCNA identified gene modules highly correlated to HCC. Then, ageing-highly related differentially expressed genes (AgHDEGs) were identified. Correlation analysis, GO and KEGG functional enrichment analysis, and gene co-expression network analysis further elucidated the functions of AgHDEGs. The STRING database identified hub AgHDEGs with CCNB1 subsequently evaluated for diagnostic value using ROC curve analysis. Additionally, we explored the correlation between CCNB1 and immune cells and assessed its biological functions via GSEA. Ultimately, the conclusions from bioinformatics analysis were confirmed via in vitro experiments, complemented by molecular docking simulations of gene-drug interactions.
Eight AgHDEGs (KPNA2, CCT3, CCNB1, RACGAP1, CDKN3, FEN1, MT1X and FOXM1) were identified. PPI network analysis highlighted CCNB1 as hub AgHDEGs with ROC analysis confirming its strong diagnostic potential. Analysis of immune infiltration revealed a significant correlation between CCNB1 and M0 macrophages. Subsequent studies showed CCNB1's critical role in regulating the cell cycle. Validation experiments illustrated an upregulation of CCNB1 expression in HCC, while inhibiting CCNB1 may reduce HepG2 cell proliferation by promoting cellular senescence. Moreover, molecular docking indicated CCNB1 as a potential therapeutic target.
Our study underscores CCNB1's potential impact on HCC senescence and progression, suggesting its candidacy as a biomarker for HCC.
肝细胞癌（HCC）起源于肝脏，早期通常无症状，术后常发生转移和复发。目前，缺乏可靠的HCC诊断生物标志物和治疗靶点。本研究利用生物信息学分析和体外实验，研究细胞衰老对HCC的影响，以确定潜在的生物标志物。
我们整合了来自GEO微阵列（GSE14520、GSE45267和GSE64041）的数据，使用R包limma分析差异表达基因（DEG）。加权基因共表达网络分析（WGCNA）确定了与HCC高度相关的基因模块。然后，鉴定了衰老高度相关的差异表达基因（AgHDEG）。相关性分析、基因本体（GO）和京都基因与基因组百科全书（KEGG）功能富集分析以及基因共表达网络分析进一步阐明了AgHDEG的功能。STRING数据库确定了关键AgHDEG，随后使用ROC曲线分析评估其诊断价值。此外，我们探讨了CCNB1与免疫细胞之间的相关性，并通过基因集富集分析（GSEA）评估其生物学功能。最终，通过体外实验证实了生物信息学分析的结论，并辅以基因-药物相互作用的分子对接模拟。
鉴定出8个AgHDEG（KPNA2、CCT3、CCNB1、RACGAP1、CDKN3、FEN1、MT1X和FOXM1）。蛋白质-蛋白质相互作用（PPI）网络分析突出显示CCNB1为关键AgHDEG，ROC分析证实其具有强大的诊断潜力。免疫浸润分析显示CCNB1与M0巨噬细胞之间存在显著相关性。随后的研究表明CCNB1在调节细胞周期中起关键作用。验证实验表明HCC中CCNB1表达上调，而抑制CCNB1可能通过促进细胞衰老来降低HepG2细胞增殖。此外，分子对接表明CCNB1是一个潜在的治疗靶点。
我们的研究强调了CCNB1对HCC衰老和进展的潜在影响，表明其有作为HCC生物标志物的潜力。
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