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Relevance network between chemosensitivity and transcriptome in human hepatoma cells.
Masaru Moriyama1, Yujin Hoshida, Motoyuki Otsuka
1Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan. moriyamamint@h.u-tokyo.ac.jp
Molecular Cancer Therapeutics
|February 18, 2003
Summary
Hepatoma cells show resistance to chemotherapy, often linked to gene expression, particularly transporters. Understanding these gene-drug interactions can improve cancer treatment strategies.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Hepatoma (liver cancer) generally exhibits poor response to chemotherapy.
- Mechanisms underlying anticancer drug resistance in hepatoma are not fully understood.
Purpose of the Study:
- To comprehensively evaluate the relationship between gene expression profiles and chemosensitivity in human hepatoma cells.
- To identify specific genes and pathways associated with drug resistance using network analysis.
Main Methods:
- Utilized cDNA microarray to measure baseline expression of 2300 genes in eight hepatoma cell lines.
- Determined chemosensitivity by measuring drug concentrations for 50% growth inhibition (GI50) for eight anticancer drugs.
- Constructed relevance networks to analyze correlations between gene expression and chemosensitivity.
Main Results:
- Identified 52 significant gene-expression correlations with chemosensitivity, involving 42 genes.
- Transporter genes, particularly those negatively correlated with chemosensitivity, were prominent (nearly 20%).
- Specific correlations found: Transporter associated with antigen processing 1 with mitoxantrone resistance; topoisomerase II beta with doxorubicin/epirubicin resistance; superoxide dismutase 2 with nimustine response.
Conclusions:
- Gene expression, especially transporter systems, plays a significant role in hepatoma drug resistance.
- Network analysis revealed correlations missed by traditional clustering methods.
- Findings provide insights for developing strategies to overcome chemotherapy resistance in liver cancer.