PURPOSE: Predominant causes of @entity135 recurrence after radiotherapy are rapid repopulation, @entity519 , fraction of @entity5 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 biologic processes that could be targeted to overcome intrinsic resistance. EXPERIMENTAL DESIGN: We analyzed both microRNA and mRNA expression in a large panel of @entity213 ( @entity213 ) cell lines. Expression was measured on both irradiated and unirradiated samples. Results were validated using modified cell lines and a series of @entity1 with @entity5 . 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 @entity20157 ( @entity20157 ) was shown to correlate with @entity66 recurrence after radiotherapy in a series of @entity1 with @entity5 . CONCLUSIONS: These findings indicate that EMT and low expression of EMT-inhibiting miRs, especially @entity20157 , measured in pretreatment material, causes intrinsic radioresistance of @entity213 , which could enable identification and treatment modification of radioresistant @entity5 . Clin Cancer Res; 21(24); 5630-8.   2015 AACR.

Pretreatment microRNA Expression Impacting on Epithelial-to-Mesenchymal Transition Predicts Intrinsic Radiosensitivity in @entity135 Cell Lines and XXXX .

@entity1 :: ('9606', 'Species') :: ['patients'] @entity135 :: ('MESH:D006258', 'Disease') :: ['head and neck cancer'] @entity20157 :: ('406986', 'Gene') :: ['miR-203', 'miR'] @entity66 :: ('MESH:D004194', 'Disease') :: ['local disease'] @entity5 :: ('MESH:D009369', 'Disease') :: ['laryngeal cancer', 'cancer', 'tumors'] @entity519 :: ('MESH:D000860', 'Disease') :: ['hypoxia'] @entity213 :: ('MESH:C535575', 'Disease') :: ['head and neck squamous cell carcinoma', 'HNSCC']
@entity1 :: (9606,Species) :: ['Patients']
