Differential gene expression before and after ionizing radiation of subcutaneous fibroblasts identifies breast cancer patients resistant to radiation-induced fibrosis.
OBJECTIVE
Differentially gene expression between patients with either very low or very high risk of radiation-induced fibrosis (RIF) in patient-derived fibroblasts after irradiation has previously been reported. In the present study, we are investigating the robustness of radiation-induced changes in gene expression in fibroblasts, whether differential expression is more pronounced when looking at the fold induction levels, taking into account the differences in background expression levels between patients, and whether there is a linear correlation between individual risk of RIF and changes in radiation-induced gene expression in fibroblasts.


METHODS
Gene expression was analysed by quantitative real-time PCR before and after a fractionated scheme with 3x3.5Gy/3 days in fibroblasts derived from 26 patients with breast cancer treated with post-mastectomy radiotherapy.


RESULTS
Robust radiation-induced changes in gene expression were observed, with differential gene expression between low and high risk patients being most pronounced for the fold induction level ('after' value divided by 'before' value for each patient). When including patients with intermediate risk, there was no linear correlation between individual risk of RIF and differential expression of the genes investigated. Rather, differential gene expression could divide patients into two clearly separated groups, a larger, sensitive group and a smaller resistant group.


CONCLUSIONS
Differential gene expression in irradiated fibroblasts might be an important tool in the identification of differences in the genetic background between patients with variable risk of RIF, and in the identification of new targets for prevention and intervention of the fibrotic process.
Alsner
Jan
J
Department of Experimental Clinical Oncology, Aarhus University Hospital, Denmark. jan@oncology.dk
Rødningen
Olaug K
OK
Overgaard
Jens
J
D001943:Breast Neoplasms / Q000473:pathology / Q000532:radiotherapy; D002478:Cells, Cultured; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects*; D005355:Fibrosis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D006801:Humans; D016133:Polymerase Chain Reaction / Q000379:methods; D011836:Radiation Tolerance; D011839:Radiation, Ionizing; D040521:Subcutaneous Tissue / Q000378:metabolism / Q000528:radiation effects*