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Published on: December 7, 2019
Microarray-based Prediction of Cytotoxicity of Tumor Cells to Arsenic Trioxide
1Center for Molecular Biology, University of Heidelberg, Im Neuenheimer Feld 282, 69120 Heidelberg.
Abstract:
Arsenic has been used since ancient times as a medicinal agent. Currently, arsenic trioxide is experiencing a thriving revival in modern oncology. The aim of this study was to identify the molecular predictors of sensitivity and resistance to arsenic trioxide. We mined the microarray database of the National Cancer Institute (NCI), USA, for genes whose expression correlated with the IC50 values for arsenic trioxide of 60 cell lines of different tumor types. By COMPARE analysis, Kendall's τ test, and false discovery rate (FDR) analyses, 47 out of 9706 genes or expressed sequence tags (ESTs) were identified. If the mRNA expression of the 47 genes or ESTs was subjected to hierarchical cluster analysis and cluster image mapping, sensitivity or resistance of the 60 cell lines to arsenic trioxide was predictable with statistical significance (p=1.01 × 10-5). While the proteins encoded by the 47 genes identified differ in their specific functions (signal transducers, transcription factors, proteasome degradation proteins, proliferation-related proteins, regulators of oxidative stress etc.), it is intriguing that many of them are in one way or another involved in the apoptotic machinery, indicating that apoptosis is an important mechanism of arsenic trioxide's cytotoxicity.
Insights
Arsenic trioxide shows promise in cancer treatment. Researchers identified 47 genes predicting sensitivity or resistance, highlighting apoptosis as a key mechanism for arsenic trioxide
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Arsenic compounds have historical medicinal uses.
- Arsenic trioxide is re-emerging as a vital anti-cancer agent.
- Understanding molecular predictors of arsenic trioxide response is crucial.
Purpose of the Study:
- To identify molecular markers predicting sensitivity and resistance to arsenic trioxide.
- To analyze gene expression patterns in relation to arsenic trioxide efficacy.
- To explore the role of gene expression in predicting treatment outcomes.
Main Methods:
- Utilized the National Cancer Institute's microarray database.
- Analyzed gene expression data from 60 diverse cancer cell lines.
- Employed statistical analyses including COMPARE, Kendall's τ test, and FDR analysis.
Main Results:
- Identified 47 genes/ESTs significantly correlating with arsenic trioxide IC50 values.
- Hierarchical clustering and cluster image mapping predicted sensitivity/resistance with statistical significance (p=1.01 × 10-5).
- Identified genes encode diverse proteins involved in cellular processes, notably apoptosis.
Conclusions:
- Gene expression profiling can predict cellular response to arsenic trioxide.
- Apoptosis is a significant mechanism underlying arsenic trioxide's anti-cancer effects.
- The identified genes offer potential biomarkers for arsenic trioxide therapy.
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