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基于网络的肝细胞癌候选致癌基因和信号通路分析

Network-based analysis of candidate oncogenes and pathways in hepatocellular carcinoma.

作者信息

Rahimi-Farsi Nasim, Shahbazi Taha, Ghorbani Abozar, Mottaghi-Dastjerdi Negar, Yazdani Fateme, Mohseni Parvin, Guzzi Pietro Hiram, Esmail Nia Gita, Shahbazi Behzad, Ahmadi Khadijeh

机构信息

Department of Biology, University College of Nabi Akram, Tabriz, Iran.

Neurosurgery Research Group (NRG), Razi Hospital, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Biochem Biophys Rep. 2025 Jun 10;43:102086. doi: 10.1016/j.bbrep.2025.102086. eCollection 2025 Sep.

Abstract

Hepatocellular carcinoma (HCC) is a major worldwide health burden due to poor outcomes. Identifying dysregulated molecular circuits in HCC is critical for developing precise treatments. A systems-level approach using multi-omics data is required to reveal the intricate non-linear interactions underlying liver carcinogenesis. Both tumor and control tissues contained differentially expressed genes (DEGs). Hub genes with the strongest connection were identified as potential drivers. Protein-protein interaction (PPI) mapping verified hub connectivity. Perturbed functions were evaluated using Gene Ontology and KEGG pathway enrichment analysis. Cytoscape clustering separated the interactome into modules. Motif discovery indicated a shift in -regulatory logic. Expression analysis, survival analysis, and drug screening were performed on the hub genes. Network hub gene analysis identified 11 hub genes, including DLGAP5, KIF23, KIF11, CCNB1, CDK1, BRCA1, CCNA2, SHCBP1, KIAA0101, FAM83D, and SPC25. Gene set enrichment analysis (GSEA) revealed dysregulation in cell cycle progression, DNA damage response, and metabolic pathways, and an association of these genes with reduced overall survival in HCC patients. Also, drug screening identified potential therapeutic agents targeting these hub genes.The findings increase mechanistic understanding with potential clinical applications. Future validation studies that include multi-omic data may strengthen current hypotheses and enable targeted therapy design against crucial in HCC.

摘要

肝细胞癌(HCC)由于预后较差,是全球主要的健康负担。识别HCC中失调的分子回路对于开发精准治疗至关重要。需要一种使用多组学数据的系统水平方法来揭示肝癌发生背后复杂的非线性相互作用。肿瘤组织和对照组织均含有差异表达基因(DEG)。具有最强连接的枢纽基因被确定为潜在驱动因素。蛋白质-蛋白质相互作用(PPI)图谱验证了枢纽连接性。使用基因本体论和KEGG通路富集分析评估受干扰的功能。Cytoscape聚类将相互作用组分离为模块。基序发现表明调控逻辑发生了转变。对枢纽基因进行了表达分析、生存分析和药物筛选。网络枢纽基因分析确定了11个枢纽基因,包括DLGAP5、KIF23、KIF11、CCNB1、CDK1、BRCA1、CCNA2、SHCBP1、KIAA0101、FAM83D和SPC25。基因集富集分析(GSEA)揭示了细胞周期进程、DNA损伤反应和代谢途径的失调,以及这些基因与HCC患者总生存期降低的关联。此外,药物筛选确定了靶向这些枢纽基因的潜在治疗药物。这些发现增加了对其机制的理解,并具有潜在的临床应用价值。未来包括多组学数据的验证研究可能会加强当前的假设,并实现针对HCC关键因素的靶向治疗设计。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35ef/12182303/4e1ed75dfc80/ga1.jpg

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