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.

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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