title: Serum Proteome Signature of Radiation Response: Upregulation of Inflammation-Related Factors and Downregulation of Apolipoproteins and Coagulation Factors in Cancer Patients Treated With Radiation Therapy--A Pilot Study.
abstract: OBJECTIVE
  Ionizing radiation affects the proteome of irradiated cells and tissue, yet data concerning changes induced during radiation therapy (RT) in human blood are fragmentary and inconclusive. We aimed to identify features of serum proteome and associated processes involved in response to partial body irradiation during cancer treatment.
  
  
  METHODS
  Twenty patients with head and neck squamous cell cancer (HNSCC) and 20 patients with prostate cancer received definitive intensity modulated RT. Blood samples were collected before RT, just after RT, and 1 month after the end of RT. Complete serum proteome was analyzed in individual samples, using a shotgun liquid chromatography-tandem mass spectrometry approach which allowed identification of approximately 450 proteins. Approximately 100 unique proteins were quantified in all samples after exclusion of immunoglobulins, and statistical significance of differences among consecutive samples was assessed. Processes associated with quantified proteins and their functional interactions were predicted using gene ontology tools.
  
  
  RESULTS
  RT-induced changes were marked in the HNSCC patient group: 22 upregulated and 33 downregulated proteins were detected in post-RT sera. Most of the changes reversed during follow-up, yet levels of some proteins remained affected 1 month after the end of RT. RT-upregulated proteins were associated with acute phase, inflammatory response, and complement activation. RT-downregulated proteins were associated with transport and metabolism of lipids (plasma apolipoproteins) and blood coagulation. RT-induced changes were much weaker in prostate cancer patients, which corresponded to differences in acute radiation toxicity observed in both groups. Nevertheless, general patterns of RT-induced sera proteome changes were similar in both of the groups of cancer patients.
  
  
  CONCLUSIONS
  In this pilot study, we proposed to identify a molecular signature of radiation response, based on specific features of serum proteome. The signature included upregulation of factors involved in acute or inflammatory response but also downregulation of plasma apolipoproteins and factors involved in blood coagulation.
authors.affiliation: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland. Electronic address: widlak@io.gliwice.pl.
authors.forename: Piotr
authors.initials: P
authors.lastname: Widlak
authors.affiliation: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
authors.forename: Karol
authors.initials: K
authors.lastname: Jelonek
authors.affiliation: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Wojakowska
authors.affiliation: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Pietrowska
authors.affiliation: Institute of Automatics Control, Silesian University of Technology, Gliwice, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Polanska
authors.affiliation: Institute of Bioorganic Chemistry of the Polish Academy of Sciences, Poznan, Poland.
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Marczak
authors.affiliation: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
authors.forename: Leszek
authors.initials: L
authors.lastname: Miszczyk
authors.affiliation: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Składowski
mesh_terms: D000230:Adenocarcinoma / Q000097:blood* / Q000473:pathology / Q000532:radiotherapy; D000368:Aged; D000369:Aged, 80 and over; D001779:Blood Coagulation Factors / Q000032:analysis / Q000378:metabolism / Q000528:radiation effects*; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000473:pathology / Q000532:radiotherapy; D015536:Down-Regulation; D006258:Head and Neck Neoplasms / Q000097:blood* / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood*; D010865:Pilot Projects; D011471:Prostatic Neoplasms / Q000097:blood* / Q000473:pathology / Q000532:radiotherapy; D020543:Proteome / Q000032:analysis / Q000378:metabolism / Q000528:radiation effects*; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects*; D015854:Up-Regulation
chemical_list: D001779:Blood Coagulation Factors; D008074:Lipoproteins; D009363:Neoplasm Proteins; D020543:Proteome