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Open Access Green as soon as Postprint is submitted to ZB.
Unique proteomic signature for radiation sensitive patients: A comparative study between normo-sensitive and radiation sensitive breast cancer patients.
Mutat. Res. -Fund. Mol. Mech. Mutag. 776, 128-135 (2015)
Radiation therapy is a cornerstone of modern cancer treatment. Understanding the mechanisms behind normal tissue sensitivity is essential in order to minimize adverse side effects and yet to prevent local cancer reoccurrence. The aim of this study was to identify biomarkers of radiation sensitivity to enable personalized cancer treatment.To investigate the mechanisms behind radiation sensitivity a pilot study was made where eight radiation-sensitive and nine normo-sensitive patients were selected from a cohort of 2914 breast cancer patients, based on acute tissue reactions after radiation therapy. Whole blood was sampled and irradiated in vitro with 0, 1, or 150. mGy followed by 3. h incubation at 37. °C. The leukocytes of the two groups were isolated, pooled and protein expression profiles were investigated using isotope-coded protein labeling method (ICPL). First, leukocytes from the in vitro irradiated whole blood from normo-sensitive and extremely sensitive patients were compared to the non-irradiated controls. To validate this first study a second ICPL analysis comparing only the non-irradiated samples was conducted. Both approaches showed unique proteomic signatures separating the two groups at the basal level and after doses of 1 and 150. mGy.Pathway analyses of both proteomic approaches suggest that oxidative stress response, coagulation properties and acute phase response are hallmarks of radiation sensitivity supporting our previous study on oxidative stress response. This investigation provides unique characteristics of radiation sensitivity essential for individualized radiation therapy.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Biomarker ; Breast Cancer ; Low-dose Radiation ; Proteomics ; Radiosensitivity ; Radiotherapy; Ionizing-radiation; Hydrogen-peroxide; Oxidative Stress; Reactive Oxygen; Nucleotide Pool; Gamma-radiation; Radiotherapy; Target; Tissue; Cells
ISSN (print) / ISBN
0027-5107
e-ISSN
1873-135X
Quellenangaben
Volume: 776,
Pages: 128-135
Publisher
Elsevier
Publishing Place
Amsterdam
Non-patent literature
Publications
Reviewing status
Peer reviewed