title: Baseline plasma proteomic analysis to identify biomarkers that predict radiation-induced lung toxicity in patients receiving radiation for non-small cell lung cancer.
abstract: OBJECTIVE
  To identify new plasma proteomic markers before radiotherapy start to predict later grade ≥2 radiation-induced lung toxicity (RILT2).
  
  
  METHODS
  Fifty-seven patients with non-small cell lung cancer received radiotherapy (RT) were eligible. Forty-eight patients with minimum follow-up of 1 year, nine with RILT2 with tumor stage matched to 39 without RILT2, were enrolled for this analysis. Platelet-poor plasma was obtained within 2 weeks before radiotherapy. The plasma proteomes were compared using a multiplexed quantitative proteomics approach involving ExacTag labeling, reverse-phase high-performance liquid chromatography, and nano liquid chromatography electrospray ionization tandem mass spectrometry. Z scores and Bonferroni-adjusted p values for the two-sample mean comparison were used to identify the differential protein expression between patients with and without RILT2.
  
  
  RESULTS
  More than 200 proteins were identified and quantified. After excluding proteins that were not detected in at least 40% of the 48 patient samples, C4b-binding protein alpha chain and vitronectin had significantly higher (p < 0.001 and p = 0.02) expression levels in patients with RILT2 compared with patients without RILT2. These two proteins were validated by Western blot. Ingenuity pathway analysis revealed that they both play important roles in the inflammatory response and are associated with the known pathways of radiation-induced lung damage.
  
  
  CONCLUSIONS
  This proteomic approach demonstrates new plasma protein biomarkers before treatment for future studies on RILT2 prediction.
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Xu-Wei
authors.initials: XW
authors.lastname: Cai
authors.forename: Kerby A
authors.initials: KA
authors.lastname: Shedden
authors.forename: Shang-Hu
authors.initials: SH
authors.lastname: Yuan
authors.forename: Mary A
authors.initials: MA
authors.lastname: Davis
authors.forename: Lu-Ying
authors.initials: LY
authors.lastname: Xu
authors.forename: Cong-Ying
authors.initials: CY
authors.lastname: Xie
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Fu
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Lawrence
authors.forename: David M
authors.initials: DM
authors.lastname: Lubman
authors.forename: Feng-Ming Spring
authors.initials: FM
authors.lastname: Kong
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000473:pathology / Q000532:radiotherapy; D050716:Complement C4b-Binding Protein / Q000032:analysis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008168:Lung / Q000528:radiation effects*; D008175:Lung Neoplasms / Q000097:blood* / Q000473:pathology / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011446:Prospective Studies; D011506:Proteins / Q000032:analysis*; D040901:Proteomics / Q000379:methods*; D011832:Radiation Injuries / Q000097:blood* / Q000175:diagnosis; D015203:Reproducibility of Results; D019096:Vitronectin / Q000097:blood
chemical_list: D015415:Biomarkers; D050716:Complement C4b-Binding Protein; D011506:Proteins; D019096:Vitronectin