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Published on: May 11, 2016
Identification of deregulation mechanisms specific to cancer subtypes
Magali Champion1, Julien Chiquet2, Pierre Neuvial3
1Université de Paris, CNRS, MAP5 UMR8145, Paris, France.
Abstract:
In many cancers, mechanisms of gene regulation can be severely altered. Identification of deregulated genes, which do not follow the regulation processes that exist between transcription factors and their target genes, is of importance to better understand the development of the disease. We propose a methodology to detect deregulation mechanisms with a particular focus on cancer subtypes. This strategy is based on the comparison between tumoral and healthy cells. First, we use gene expression data from healthy cells to infer a reference gene regulatory network. Then, we compare it with gene expression levels in tumor samples to detect deregulated target genes. We finally measure the ability of each transcription factor to explain these deregulations. We apply our method on a public bladder cancer data set derived from The Cancer Genome Atlas project and confirm that it captures hallmarks of cancer subtypes. We also show that it enables the discovery of new potential biomarkers.
Insights
This study introduces a new method to find altered gene regulation in cancer by comparing tumor and healthy cells. The approach identifies deregulated genes and transcription factors, aiding in understanding cancer development and discovering biomarkers.
Area of Science:
- Genomics
- Bioinformatics
- Cancer Biology
Background:
- Gene regulation is often altered in cancer, impacting disease development.
- Identifying deregulated genes is crucial for understanding cancer mechanisms.
- Transcription factors play a key role in gene regulation.
Purpose of the Study:
- To develop a methodology for detecting gene deregulation mechanisms in cancer subtypes.
- To identify deregulated target genes and transcription factors by comparing tumor and healthy cells.
- To assess the utility of the method in a bladder cancer dataset.
Main Methods:
- Inferring a reference gene regulatory network from healthy cell gene expression data.
- Comparing gene expression in tumor samples to the reference network to detect deregulated genes.
- Quantifying the ability of transcription factors to explain observed gene deregulations.
Main Results:
- The methodology successfully identified deregulated genes and transcription factors in cancer.
- Application to a bladder cancer dataset revealed cancer subtype hallmarks.
- The method demonstrated potential for discovering novel cancer biomarkers.
Conclusions:
- The proposed method effectively detects gene deregulation mechanisms in cancer subtypes.
- This approach can enhance the understanding of cancer development and progression.
- The methodology facilitates the discovery of new diagnostic and therapeutic biomarkers.
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