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Status |
Public on Mar 19, 2016 |
Title |
Pretreatment microRNA expression impacting on epithelial to mesenchymal transition predicts intrinsic radiosensitivity in head and neck cancer cell lines and patients [FaDu] |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
Purpose: Predominant causes of head and neck cancer recurrence after radiotherapy are rapid repopulation, hypoxia, fraction of cancer stem cells and intrinsic radioresistance. Currently, intrinsic radioresistance can only be assessed by ex-vivo colony assays. Besides being time-consuming, colony assays do not identify causes of intrinsic resistance. We aimed to identify a biomarker for intrinsic radioresistance to be used before start of treatment and to reveal biological processes that could be targeted to overcome intrinsic resistance. Experimental design: We analyzed both micro- and messenger RNA expression in a large panel of HNSCC cell lines. Expression was measured on both irradiated and unirradiated samples. Results were validated using modified cell lines and a series of laryngeal cancer patients. Results: MiRs, mRNAs and gene sets that correlated with resistance could be identified from expression data of unirradiated cells. The presence of epithelial to mesenchymal transition (EMT) and low expression of miRs involved in the inhibition of EMT were important radioresistance determinants. This finding was validated in two independent cell line pairs, in which the induction of EMT reduced radiosensitivity. Moreover, low expression of the most important miR (miR-203) was shown to correlate with local disease recurrence after radiotherapy in a series of laryngeal cancer patients. Conclusions: These findings indicate that EMT and low expression of EMT-inhibiting miRs, especially miR-203, measured in pre-treatment material, causes intrinsic radioresistance of HNSCC, which could enable identification and treatment modification of radioresistant tumors.
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Overall design |
To test if the induction of epithelial to mesenchymal transition increases radioresistance, these cell lines were obtained from prof. Kou-Juey Wu (National Yang-Ming University, Taiwan) and tested. Detailed information about development of the cell lines can be read from the original publication (PMID:18297062).
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Contributor(s) |
de Jong MC, tenHoeve JJ, Grénman R, Wessels LF, Kerkhoven R, te Riele H, van den Brekel MW, Verheij M, Begg AC |
Citation(s) |
26265694 |
Submission date |
Mar 18, 2016 |
Last update date |
Feb 18, 2019 |
Contact name |
Monique C. de Jong |
E-mail(s) |
m.d.jong@nki.nl
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Organization name |
Netherlands Cancer Institute
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Department |
Dept of Biological Stress Response and Dept. of Radiation Oncology
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Street address |
Plesmanlaan 121
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City |
Amsterdam |
ZIP/Postal code |
1066 CX |
Country |
Netherlands |
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Platforms (1) |
GPL6884 |
Illumina HumanWG-6 v3.0 expression beadchip |
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Samples (2) |
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This SubSeries is part of SuperSeries: |
GSE79372 |
Pretreatment microRNA Expression Impacting on Epithelial-to-Mesenchymal Transition Predicts Intrinsic Radiosensitivity in Head and Neck Cancer Cell Lines and Patients |
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Relations |
BioProject |
PRJNA315630 |