title: Unique proteomic signature for radiation sensitive patients; a comparative study between normo-sensitive and radiation sensitive breast cancer patients.
abstract: 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.
authors.affiliation: Center for Radiation Protection Research, Department of Molecular Biosciences, The Wernner-Gren Institute, Stockholm University, Stockholm, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Skiöld
authors.affiliation: Institute of Radiation Biology, German Research Center for Environmental Health, Helmholtz Zentrum München, Germany.
authors.forename: Omid
authors.initials: O
authors.lastname: Azimzadeh
authors.affiliation: Research Unit Protein Science, German Research Center for Environmental Health, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Merl-Pham
authors.affiliation: Division of Radiotherapy, Radiumhemmet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Ingemar
authors.initials: I
authors.lastname: Naslund
authors.affiliation: Division of Radiotherapy, Radiumhemmet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Wersall
authors.affiliation: Division of Radiotherapy, Radiumhemmet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Lidbrink
authors.affiliation: Institute of Radiation Biology, German Research Center for Environmental Health, Helmholtz Zentrum München, Germany.
authors.forename: Soile
authors.initials: S
authors.lastname: Tapio
authors.affiliation: Center for Radiation Protection Research, Department of Molecular Biosciences, The Wernner-Gren Institute, Stockholm University, Stockholm, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Harms-Ringdahl
authors.affiliation: Center for Radiation Protection Research, Department of Molecular Biosciences, The Wernner-Gren Institute, Stockholm University, Stockholm, Sweden. Electronic address: Siamak.Haghdoost@su.se.
authors.forename: Siamak
authors.initials: S
authors.lastname: Haghdoost
mesh_terms: D001943:Breast Neoplasms / Q000097:blood / Q000532:radiotherapy; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood*; D018384:Oxidative Stress / Q000528:radiation effects*; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics; D011836:Radiation Tolerance; D012189:Retrospective Studies
chemical_list: D009363:Neoplasm Proteins; D020543:Proteome
keywords: Biomarker; Breast cancer; Low-dose radiation; Proteomics; Radiosensitivity; Radiotherapy