Research article

Distinctive serum protein profiles involving abundant proteins in lung cancer patients based upon antibody microarray analysis

Wei-Min Gao^1,2 , Rork Kuick³ , Randal P Orchekowski⁴ , David E Misek³ , Ji Qiu^3,6 , Alissa K Greenberg⁵ , William N Rom⁵ , Dean E Brenner¹ , Gilbert S Omenn¹ , Brian B Haab⁴ and Samir M Hanash^3,6

¹  Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA

²  Department of Critical Care Medicine, Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA 15260, USA

³  Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109, USA

⁴  Van Andel Research Institute, Grand Rapids, MI 49503, USA

⁵  Division of Pulmonary and Critical Care Medicine, NYU Cancer Institute, NYU School of Medicine NY, NY 10016, USA

⁶  Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA

author email corresponding author email

BMC Cancer 2005, 5:110doi:10.1186/1471-2407-5-110

Published:	23 August 2005

Abstract

Background

Cancer serum protein profiling by mass spectrometry has uncovered mass profiles that are potentially diagnostic for several common types of cancer. However, direct mass spectrometric profiling has a limited dynamic range and difficulties in providing the identification of the distinctive proteins. We hypothesized that distinctive profiles may result from the differential expression of relatively abundant serum proteins associated with the host response.

Methods

Eighty-four antibodies, targeting a wide range of serum proteins, were spotted onto nitrocellulose-coated microscope slides. The abundances of the corresponding proteins were measured in 80 serum samples, from 24 newly diagnosed subjects with lung cancer, 24 healthy controls, and 32 subjects with chronic obstructive pulmonary disease (COPD). Two-color rolling-circle amplification was used to measure protein abundance.

Results

Seven of the 84 antibodies gave a significant difference (p < 0.01) for the lung cancer patients as compared to healthy controls, as well as compared to COPD patients. Proteins that exhibited higher abundances in the lung cancer samples relative to the control samples included C-reactive protein (CRP; a 13.3 fold increase), serum amyloid A (SAA; a 2.0 fold increase), mucin 1 and α-1-antitrypsin (1.4 fold increases). The increased expression levels of CRP and SAA were validated by Western blot analysis. Leave-one-out cross-validation was used to construct Diagonal Linear Discriminant Analysis (DLDA) classifiers. At a cutoff where all 56 of the non-tumor samples were correctly classified, 15/24 lung tumor patient sera were correctly classified.

Conclusion

Our results suggest that a distinctive serum protein profile involving abundant proteins may be observed in lung cancer patients relative to healthy subjects or patients with chronic disease and may have utility as part of strategies for detecting lung cancer.