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Open Access Short report

Constitutive gene expression profile segregates toxicity in locally advanced breast cancer patients treated with high-dose hyperfractionated radical radiotherapy

Luis Alberto Henríquez Hernández123*, Pedro Carlos Lara24, Beatriz Pinar24, Elisa Bordón2, Carlos Rodríguez Gallego25, Cristina Bilbao2, Leandro Fernández Pérez23 and Amílcar Flores Morales6

Author Affiliations

1 Canary Foundation of Investigation and Health (FUNCIS), Spain

2 Canary Institute for Cancer Research (ICIC), Spain

3 Clinic Sciences Department of Las Palmas de Gran Canaria University (ULPGC), Spain

4 Radiation Oncology Department, Hospital Universitario de Gran Canaria Dr Negrín, Spain

5 Inmunology Department, Hospital Universitario de Gran Canaria Dr Negrín, Spain

6 Molecular Endocrinology Group, Center for Molecular Medicine, Karolinska Intitute, Stockholm, Sweden

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Radiation Oncology 2009, 4:17  doi:10.1186/1748-717X-4-17

Published: 4 June 2009

Abstract

Breast cancer patients show a wide variation in normal tissue reactions after radiotherapy. The individual sensitivity to x-rays limits the efficiency of the therapy. Prediction of individual sensitivity to radiotherapy could help to select the radiation protocol and to improve treatment results. The aim of this study was to assess the relationship between gene expression profiles of ex vivo un-irradiated and irradiated lymphocytes and the development of toxicity due to high-dose hyperfractionated radiotherapy in patients with locally advanced breast cancer. Raw data from microarray experiments were uploaded to the Gene Expression Omnibus Database http://www.ncbi.nlm.nih.gov/geo/ webcite (GEO accession GSE15341). We obtained a small group of 81 genes significantly regulated by radiotherapy, lumped in 50 relevant pathways. Using ANOVA and t-test statistical tools we found 20 and 26 constitutive genes (0 Gy) that segregate patients with and without acute and late toxicity, respectively. Non-supervised hierarchical clustering was used for the visualization of results. Six and 9 pathways were significantly regulated respectively. Concerning to irradiated lymphocytes (2 Gy), we founded 29 genes that separate patients with acute toxicity and without it. Those genes were gathered in 4 significant pathways. We could not identify a set of genes that segregates patients with and without late toxicity. In conclusion, we have found an association between the constitutive gene expression profile of peripheral blood lymphocytes and the development of acute and late toxicity in consecutive, unselected patients. These observations suggest the possibility of predicting normal tissue response to irradiation in high-dose non-conventional radiation therapy regimens. Prospective studies with higher number of patients are needed to validate these preliminary results.