Genistein is a type of isoflavone, which has been widely described as an antitumor agent in many cancers. The present study aimed to provide information on the mechanisms of genistein's activity and thus enable a wider range of targeted therapies in hepatitis B virus (HBV)-related liver cancer. We searched the DrugBank database for direct targets of genistein, which were then analyzed through the STRING (Search Tool for the Retrieval of Interacting Genes/Proteins) database to predict their secondary protein targets. Thirteen primary protein targets of genistein and 209 secondary protein targets-associated genes were identified. The data were integrated into the network of protein targets-associated genes and visualized with the Cytoscape software. We further carried out GO (Gene Ontology) analysis and KEGG (Kyoto Encyclopedia of Gene and Genome) pathway analysis using DAVID (database for annotation, visualization, and integrated discovery) tool. The top 14 KEGG pathways were further assessed, and 19 overlapping genes derived from pathways of hepatitis B and cancer were discovered. The overlapping targets were further mapped in the online tool UALCAN to evaluate the survival rate of hepatocellular carcinoma (HCC) patients. We found that the overexpression of Grb2 (growth factor receptor-binding protein 2) (p < 0.0001) was linked to poor overall survival for liver HCC patients, followed by AKT1 (p = 0.0015) and PIK3CA (p = 0.0088). The present study analyzes the drug-target-disease network and may prove to be a useful tool in gene-phenotype connectivity for genistein in HBV-related liver cancer. Our data also pave the way for further research on Grb2 during the development of chronic HBV infection in liver cancer.

中文翻译：

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染料木素维持的基因-表型连接的药物-靶标相互作用网络分析

染料木黄酮是一种异黄酮，已被广泛描述为许多癌症中的抗肿瘤剂。本研究旨在提供关于染料木黄酮活性机制的信息，从而为乙型肝炎病毒 (HBV) 相关的肝癌提供更广泛的靶向治疗。我们在 DrugBank 数据库中搜索了染料木黄酮的直接靶标，然后通过 STRING（用于检索相互作用基因/蛋白质的搜索工具）数据库进行分析，以预测其二级蛋白质靶标。确定了染料木素的 13 个主要蛋白质靶标和 209 个二级蛋白质靶标相关基因。数据被整合到蛋白质靶标相关基因的网络中，并用 Cytoscape 软件进行可视化。我们使用 DAVID（用于注释、可视化和集成发现的数据库）工具进一步进行了 GO（基因本体论）分析和 KEGG（京都基因和基因组百科全书）通路分析。进一步评估了前14条KEGG通路，发现了来自乙肝和癌症通路的19个重叠基因。在在线工具 UALCAN 中进一步映射了重叠的目标，以评估肝细胞癌 (HCC) 患者的存活率。我们发现 Grb2（生长因子受体结合蛋白 2）的过度表达（在在线工具 UALCAN 中进一步映射了重叠的目标，以评估肝细胞癌 (HCC) 患者的存活率。我们发现 Grb2（生长因子受体结合蛋白 2）的过度表达（在在线工具 UALCAN 中进一步映射了重叠的目标，以评估肝细胞癌 (HCC) 患者的存活率。我们发现 Grb2（生长因子受体结合蛋白 2）的过度表达（p < 0.0001) 与肝 HCC 患者的总体生存率较差有关，其次是 AKT1 ( p  = 0.0015) 和 PIK3CA ( p  = 0.0088)。本研究分析了药物-靶点-疾病网络，可能被证明是 HBV 相关肝癌中金雀异黄素基因表型连接的有用工具。我们的数据也为进一步研究 Grb2 在肝癌慢性 HBV 感染的发展过程中铺平了道路。