Cancer and ionizing radiation exposure are associated with inflammation. To identify a set of radiation-specific signatures of inflammation-associated genes in the blood of partially exposed radiotherapy patients, differential expression of 249 inflammatory genes was analyzed in blood samples from cancer patients and healthy individuals. The gene expression analysis on a cohort of 63 cancer patients (endometrial, head and neck, and prostate cancer) before and during radiotherapy (24 h, 48 h, ~1 week, ~4-8 weeks, and 1 month after the last fraction) identified 31 genes and 15 up- and 16 down-regulated genes. Transcription variability under normal conditions was determined using blood drawn on three separate occasions from four healthy donors. No difference in inflammatory expression between healthy donors and cancer patients could be detected prior to radiotherapy. Remarkably, repeated sampling of healthy donors revealed an individual endogenous inflammatory signature. Next, the potential confounding effect of concomitant inflammation was studied in the blood of seven healthy donors taken before and 24 h after a flu vaccine or ex vivo LPS (lipopolysaccharide) treatment; flu vaccination was not detected at the transcriptional level and LPS did not have any effect on the radiation-induced signature identified. Finally, we identified a radiation-specific signature of 31 genes in the blood of radiotherapy patients that were common for all cancers, regardless of the immune status of patients. Confirmation via MQRT-PCR was obtained for BCL6, MYD88, MYC, IL7, CCR4 and CCR7. This study offers the foundation for future research on biomarkers of radiation exposure, radiation sensitivity, and radiation toxicity for personalized radiotherapy treatment.

Biomedical Research Centre University Hospital Hradec Králové 500 05 Hradec Králové Czech Republic

Cancer Mechanisms and Biomarkers Group Centre for Radiation Chemical and Environmental Hazards UK Health Security Agency Oxfordshire OX11 0RQ UK

Clinical Research Support Centre Medical University of Gdańsk Gdańsk M Skłodowskiej Curie 3a Street 80 210 Gdańsk Poland

Department of Data Mining Silesian University of Technology 44 100 Gliwice Poland

Department of Oncology and Radiotherapy and 4th Department of Internal Medicine Hematology University Hospital 500 05 Hradec Králové Czech Republic

Department of Radiation Dosimetry Nuclear Physics Institute Czech Academy of Sciences 180 00 Prague Czech Republic

Department of Radiobiology Faculty of Military Health Sciences in Hradec Králové University of Defence 662 10 Brno Czech Republic

Institute of Hematology and Blood Transfusion 128 00 Praha Czech Republic

Maria Skłodowska Curie National Research Institute of Oncology 44 102 Gliwice Poland

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