Plasma proteomic analysis may identify new markers for radiation-induced lung toxicity in patients with non-small-cell lung cancer.
OBJECTIVE
To study whether radiation induces differential changes in plasma proteomics in patients with and without radiation-induced lung toxicity (RILT) of Grade >/=2 (RILT2).


METHODS
A total of 57 patients with NSCLC received radiation therapy (RT) were eligible. Twenty patients, 6 with RILT2 with tumor stage matched to 14 without RILT2, were enrolled for this analysis. Platelet-poor plasma was obtained before RT, at 2, 4, 6 weeks during RT, and 1 and 3 months after RT. Plasma proteomes were compared using a multiplexed quantitative proteomics approach involving ExacTag labeling, reverse-phase high-performance liquid chromatography and nano-LC electrospray tandem mass spectrometry. Variance components models were used to identify the differential protein expression between patients with and without RILT2.


RESULTS
More than 100 proteins were identified and quantified. After excluding proteins for which there were not at least 2 subjects with data for at least two time points, 76 proteins remained for this preliminary analysis. C4b-binding protein alpha chain, Complement C3, and Vitronectin had significantly higher expression levels in patients with RILT2 compared with patients without RILT2, based on both the data sets of RT start to 3 months post-RT (p < 0.01) and RT start to the end of RT (p < 0.01). The expression ratios of patients with RILT2 vs. without RILT2 were 1.60, 1.36, 1.46, and 1.66, 1.34, 1.46, for the above three proteins, respectively.


CONCLUSIONS
This proteomic approach identified new plasma protein markers for future studies on RILT prediction.
Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, MI 48108, USA.
Xu-Wei
XW
Cai
Kerby
K
Shedden
Xiaoping
X
Ao
Mary
M
Davis
Xiao-Long
XL
Fu
Theodore S
TS
Lawrence
David M
DM
Lubman
Feng-Ming Spring
FM
Kong
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000808:Angiotensinogen / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000473:pathology / Q000532:radiotherapy; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003176:Complement C3 / Q000032:analysis; D050716:Complement C4b-Binding Protein / Q000032:analysis; D005260:Female; D006801:Humans; D053531:Keratins, Type II / Q000097:blood; D008168:Lung / Q000528:radiation effects*; D008175:Lung Neoplasms / Q000097:blood* / Q000473:pathology / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D036103:Nanotechnology; D011506:Proteins / Q000032:analysis*; D040901:Proteomics / Q000379:methods*; D011832:Radiation Injuries / Q000097:blood*; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods; D019096:Vitronectin / Q000097:blood
D015415:Biomarkers; D003176:Complement C3; D050716:Complement C4b-Binding Protein; D053531:Keratins, Type II; D011506:Proteins; D019096:Vitronectin; D000808:Angiotensinogen