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Drug-Target Interaction Network Analysis of Gene-Phenotype Connectivity Maintained by Genistein
Baoshan Li1, Yi Jiang1, Jingxin Chu1
1Department of General Medicine and Geriatrics, Chongqing University Central Hospital/Chongqing Emergency Medical Center, Chongqing, China.
Abstract:
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.
Insights
Genistein, an isoflavone, shows potential against hepatitis B virus (HBV)-related liver cancer by targeting key genes. Overexpression of Grb2 (growth factor receptor-binding protein 2) is linked to poor survival in hepatocellular carcinoma (HCC) patients.
Area of Science:
- Biochemistry
- Oncology
- Virology
Background:
- Genistein, an isoflavone, exhibits antitumor properties across various cancers.
- Hepatitis B virus (HBV) infection is a significant risk factor for hepatocellular carcinoma (HCC).
- Understanding genistein's molecular mechanisms in HBV-related liver cancer is crucial for targeted therapy development.
Purpose of the Study:
- To elucidate the drug-target-disease network of genistein in HBV-related liver cancer.
- To identify potential therapeutic targets for HBV-associated HCC.
- To explore the association between genistein targets and patient survival rates.
Main Methods:
- Utilized DrugBank to identify genistein's direct targets.
- Employed STRING database for predicting secondary protein targets.
- Integrated and visualized gene-protein interaction networks using Cytoscape.
- Performed Gene Ontology (GO) and KEGG pathway analyses via DAVID.
- Assessed overlapping genes in hepatitis B and cancer pathways.
- Evaluated target gene association with HCC patient survival using UALCAN.
Main Results:
- Identified 13 primary and 209 secondary protein targets of genistein.
- Discovered 19 overlapping genes between hepatitis B and cancer pathways.
- Found that overexpression of Grb2 (growth factor receptor-binding protein 2) significantly correlates with poor overall survival in HCC patients (p < 0.0001).
- AKT1 (p = 0.0015) and PIK3CA (p = 0.0088) also showed links to reduced survival.
Conclusions:
- Genistein's complex network of targets provides insights into its efficacy in HBV-related liver cancer.
- Grb2 emerges as a critical target, potentially influencing HCC progression in the context of chronic HBV infection.
- These findings support genistein as a candidate for targeted therapies and highlight Grb2 for further investigation in HBV-associated liver cancer.
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