Baseline plasma proteomic analysis to identify biomarkers that predict radiation-induced lung toxicity in patients receiving radiation for non-small cell lung cancer

Xu Wei Cai, Kerby A. Shedden, Shang Hu Yuan, Mary A. Davis, Lu Ying Xu, Cong Ying Xie, Xiao Long Fu, Theodore S. Lawrence, David M. Lubman, Feng Ming Kong

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Purpose: 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.

Original languageEnglish (US)
Pages (from-to)1073-1078
Number of pages6
JournalJournal of Thoracic Oncology
Volume6
Issue number6
DOIs
StatePublished - Jan 1 2011

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Non-Small Cell Lung Carcinoma
Proteomics
Biomarkers
Radiation
Lung
Radiotherapy
Proteins
Complement C4b-Binding Protein
Vitronectin
Electrospray Ionization Mass Spectrometry
Reverse-Phase Chromatography
Proteome
Tandem Mass Spectrometry
Liquid Chromatography
Blood Proteins
Blood Platelets
Western Blotting
High Pressure Liquid Chromatography
Neoplasms

Keywords

  • Biomarker
  • Non-small cell lung cancer
  • Proteomics
  • Radiation-induced lung toxicity

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Baseline plasma proteomic analysis to identify biomarkers that predict radiation-induced lung toxicity in patients receiving radiation for non-small cell lung cancer. / Cai, Xu Wei; Shedden, Kerby A.; Yuan, Shang Hu; Davis, Mary A.; Xu, Lu Ying; Xie, Cong Ying; Fu, Xiao Long; Lawrence, Theodore S.; Lubman, David M.; Kong, Feng Ming.

In: Journal of Thoracic Oncology, Vol. 6, No. 6, 01.01.2011, p. 1073-1078.

Research output: Contribution to journalArticle

Cai, Xu Wei ; Shedden, Kerby A. ; Yuan, Shang Hu ; Davis, Mary A. ; Xu, Lu Ying ; Xie, Cong Ying ; Fu, Xiao Long ; Lawrence, Theodore S. ; Lubman, David M. ; Kong, Feng Ming. / Baseline plasma proteomic analysis to identify biomarkers that predict radiation-induced lung toxicity in patients receiving radiation for non-small cell lung cancer. In: Journal of Thoracic Oncology. 2011 ; Vol. 6, No. 6. pp. 1073-1078.
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AU - Yuan, Shang Hu

AU - Davis, Mary A.

AU - Xu, Lu Ying

AU - Xie, Cong Ying

AU - Fu, Xiao Long

AU - Lawrence, Theodore S.

AU - Lubman, David M.

AU - Kong, Feng Ming

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