Gene expression profiling in response to radiation treatment in breast cancer [cell lines]

Introduction: Breast radiotherapy is currently one size fits all regardless of breast cancer subtype (eg. luminal, basal). However, recent clinical data suggests that radiation response may vary significantly among subtypes. Therefore, current practice leads to over- or under-treatment of women whose tumors are more or less radiation responsive. We hypothesized that this clinical variability may be due, in part, to differences in cellular radiation response. Methods: We exposed 16 biologically-diverse breast tumor cell lines to 0 or 5GY radiation. Microarray analysis was performed on RNA harvested from those cell lines. Samples were run in triplicate. Following quality assessment, differential gene expression analysis was performed using a two-way multiplicative linear mixed-effects model. A candidate radiation response biomarkers with biologically plausible role in radiation response, were identified and confirmed at the RNA and protein level with qPCR and Western blotting assays. Induction in human breast tumors was confirmed in 32 patients with paired pre- and post-radiation tumor samples using IHC and microarray analysis. Quantification of protein was performed in a blinded manner and included positive and negative controls.

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Horton JK, Siamakpour-Reihani S, Lee CT, Zhou Y, Chen W, Geradts J, Fels DR, Hoang P, Ashcraft KA, Groth J, Kung HN, Dewhirst MW, Chi JT