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Gene expression profile of colorectal cancer HCT116 cells treated with single (2Gy) or fractionated (5 x 2Gy) doses of ionizing radiation.

ABSTRACT: Radiotherapy remains a standard treatment for colorectal cancer. The clinical significance of the conventional treatment is based on accumulated dose and usually consists of single daily irradiations of 1.8 - 2 Gy fractions. However the repopulation of cancer cells during and/or after the treatment suggests that the surviving fraction of cells acquire the radioresistance to cancer therapy. It has been determined a number of radioresistance markers, but only limited data exist on the acquisition of the resistance to fractionated radiation therapy. This research provides the genomic data of gene expression changes in colorectal cancer cell HCT116 line following single and multiple fractions of irradiation, aiming to identify particular genes associated with the effect of fractionated radiotherapy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE103178 | GEO | 2017/08/29

SECONDARY ACCESSION(S): PRJNA400451

REPOSITORIES: GEO

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Project description: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. Matched pairs of pre-treatment biopsies of 34 patients treated at The Netherlands Cancer Institute between 2002 and 2010. Patients with T2-3 laryngeal cancers, all treated with radiotherapy alone with a curative intent. The series was designed to be a matched cohort of 17 patients with local recurrences matched with 17 local cures. There were no significant differences between groups with and without local recurrence in age, gender, subsite, T-stage or treatment year.

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Gene expression profile of colorectal cancer HCT116 cells treated with single (2Gy) or fractionated (5 x 2Gy) doses of ionizing radiation.

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