Transcriptomics

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Radiation induced gene signature predicts pathologic complete response to neoadjuvant chemotherapy in breast cancer patients


ABSTRACT: Purpose:The identification of biomarkers predictive of neoadjuvant chemotherapy response in breast cancer patients would be an important advancement in personalized cancer therapy. We hypothesized that due to similarities between radiation and chemotherapy induced cellular response mechanisms, radiation responsive genes may be useful in predicting response to neoadjuvant chemotherapy. Materials and Methods: Murine p53 null breast cancer cell lines representative of the luminal, basal-like and claudin-low human breast cancer subtypes were irradiated to identify radiation responsive genes. These murine radiation induced genes were then converted to their human orthologs. These genes were then used to develop a predictor of pathologic complete response (pCR) that was validated on two independent published neoadjuvant chemotherapy data sets of genomic data with response. Results: A radiation induced gene signature consisting of 30 genes was identified on a training set of 337 human primary breast cancer tumor samples that was prognostic for survival. Mean expression of this signature was calculated for individual samples in two independent published datasets and was found to be significantly predictive of pathologic complete response. Multivariate logistic regression analysis in both independent datasets showed that this 30 gene signature added significant predictive information independent of that provided by standard clinical predictors and other gene expression based predictors of pathologic complete response. Conclusion: This study provides new biologic information regarding response to neoadjuvant chemotherapy and a means of possibly improving the prediction of pathologic complete response. reference x sample

ORGANISM(S): Mus musculus  

SUBMITTER: Charles Perou   Charles M Perou  Daniel S Oh  Maggie Cheang 

PROVIDER: E-GEOD-48073 | ArrayExpress | 2015-01-21

SECONDARY ACCESSION(S): GSE48073PRJNA208896

REPOSITORIES: GEO, ArrayExpress

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Radiation-induced gene signature predicts pathologic complete response to neoadjuvant chemotherapy in breast cancer patients.

Oh Daniel S DS   Cheang Maggie C U MC   Fan Cheng C   Perou Charles M CM  

Radiation research 20140214 2


The identification of biomarkers predictive of neoadjuvant chemotherapy response in breast cancer patients would be an important advancement in personalized cancer therapy. In this study, we hypothesized that due to similarities between radiation- and chemotherapy-induced cellular response mechanisms, radiation-responsive genes may be useful in predicting response to neoadjuvant chemotherapy. Murine p53 null breast cancer cell lines representative of the luminal, basal-like and claudin-low human  ...[more]

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