ABSTRACT The prognosis for patients with non-small cell lung cancer (NSCLC) remains poor in spite of better treatments. This relates mainly to the fact that the majority of patients present with advanced disease. There is a need to identify tools which can improve screening for lung cancer in the at risk patient population. The aim of this study was to compare the breath proteomic profile of NSCLC patients with healthy control subjects to explore the potential of new biomarkers of lung cancer. Comparative proteomic analysis of exhaled breath condensate (EBC) between 14 patients with NSCLC and 13 healthy control subjects were carried out using LTQ FT Ultra mass spectrometry and database searching to determine any unique proteins. In total, 29 unique proteins were identified using multiple protein identification algorithms. A comparison of lung cancer, smoker, and ex-smoker proteomes showed that 18 proteins were shared among the three groups. While one unique protein was found in smokers and lung cancer patients, four proteins were unique to ex-smokers. This data set provides a foundation for evaluation of these proteins from EBC as potential biomarkers for non-invasive lung cancer diagnosis.
Cite this paper
nullZ. Cheng, C. Lewis, P. Thomas and M. Raftery, "Comparative Proteomics Analysis of Exhaled Breath Condensate in Lung Cancer Patients," Journal of Cancer Therapy, Vol. 2 No. 1, 2011, pp. 1-8. doi: 10.4236/jct.2011.21001.
 A. Jemal, R. Siegel, E. Ward, Y. Hao, J. Xu, T. Murray and M. J. Thun, “Cancer Statistics,” CA Cancer Journal for Clinicians, Vol. 58, No. 2, 2008, pp. 71-96. doi:10.3322/CA.2007.0010
A. Jemal, R. Siegel, E. Ward, T. Murray, J. Xu and M. J. Thun, “Cancer Statistics,” CA Cancer Journal for Clinicians, Vol. 57, No. 1, 2007, pp. 43-66. doi:10.3322/canjclin.57.1.43
M. J. Hayat, N. Howlader, M. E. Reichman and B. K. Edwards, “Cancer Statistics, Trends, and Multiple Primary Cancer Analyses from the Surveillance, Epidemiology, and End Results (SEER) Program,” Oncologist, Vol. 12, No. 1, 2007, pp. 20-37. doi:10.1634/theoncologist.12-1-20
R. D. Petty, M. C. Nicolson, K. M. Kerr, E. Collie-Duguid and G. I. Murray, “Gene Expression Profiling in Non-small Cell Lung Cancer: From Molecular Mechanisms to Clinical Application,” Clinical Cancer Research, Vol. 10, No. 10, 2004, pp. 3237-3248. doi:10.1158/1078-0432.CCR-03-0503
M. Reck, F. Crin and Lucio, “Advances in Anti-VEGF and Anti-EGFR Therapy for Advanced Non-small Cell Lung Cancer,” Lung Cancer, Vol. 3, No. 1, 2009, pp. 1-9. doi:10.1016/j.lungcan.2008.05.015
L. L. Humphrey, S. Teutsch, M. Johnson and U. S. P. S. T. Force, “Lung Cancer Screening with Sputum Cytologic Examination, Chest Radiography and Computed Tomography: An update for the U.S. Preventive Services Task Force,” Annals of Internal Medicine, Vol. 140, No. 9, 2004, pp. 740-753.
M. F. Reed, M. Molloy, E. L. Dalton and J. A. Howington, “Survival after Resection for Lung Cancer is the Outcome that Matters,” American Journal of Surgery, Vol. 188, No. 5, 2004, pp. 598-602.
D. H. Conrad, J. Goyette and P. S. Thomas, “Proteomics as a Method for Early Detection of Cancer: A Review of Proteomics, Exhaled Breath Condensate, and Lung Cancer Screening,” Journal of General Internal Medicine, Vol. 23, Suppl. 1, 2008, pp. 78-84. doi:10.1007/s11606-007-0411-1
J. Liu and P. S. Thomas, “Exhaled Breath Condensate as a Method of Sampling Airway Nitric Oxide and Other Markers of Inflammation,” Medical Science Monitor, Vol. 11, No. 8, 2005, pp. MT53-62.
T. M. Dwyer, “Sampling Airway Surface Liquid: Non-volatiles in the Exhaled Breath Condensate,” Lung, Vol. 182, No. 4, 2004, pp. 241-250. doi:10.1007/s00408-004-2506-3
K. W. Garey, M. M. Neuhauser, R. A. Robbins, L. H. Danziger and I. Rubinstein, “Markers of Inflammation in Exhaled Breath Condensate of Young Healthy Smokers,” Chest, Vol. 125, No. 1, 2004, pp. 22-60.
E. Dalaveris, T. Kerenidi, A. Katsabeki-Katsafli, T. Kiropoulos, K. Tanou, K. I. Gourgoulianis and K. Kostikas, “VEGF, TNF-Alpha and 8-Isoprostane Levels in Exhaled Breath Condensate and Serum of Patients with Lung Cancer,” Lung Cancer, Vol. 64, No. 2, 2009, pp. 219-225. doi:10.1016/j.lungcan.2008.08.015
G. E. Carpagnano, A. Spanevello, C. Curci, F. Salerno, G. P. Palladino, O. Resta, G. Di Gioia, F. Carpagnano and M. P. Foschino Barbaro, “IL-2, TNF-alpha, and Leptin: Local Versus Systemic Concentrations in NSCLC Patients,” Oncology Research, Vol. 16, No. 8, 2007, pp. 375- 381.
J. Liu and P. S. Thomas, “Relationship between Exhaled Breath Condensate Volume and Measurements of Lung Volumes,” Respiration, Vol. 74, No. 2, 2007, pp. 142-145. doi:10.1159/000094238
M. J. Raftery, “Enrichment by Organomercurial Agarose and Identification of Cys-Containing Peptides from Yeast Cell lysates,” Analytical Chemistry, Vol. 80, No. 9, 2008, pp. 3334-3341. doi:10.1021/ac702539q
C. L. Gatlin, G. R. Kleemann, L. G. Hays, A. J. Link and J. R. Yates, “Protein Identification at the Low Femtomole Level from Silver-Stained Gels Using a New Fritless Electrospray Interface for Liquid Chromatography-Mi- Crospray and Nanospray Mass Spectrometry,” Analytical Biochemistry, Vol. 263, No. 1, 1998, pp. 93- 101. doi:10.1006/abio.1998.2809
R. M. Effros, J. Biller, B. Foss, K. Hoagland, M. B. Dunning, D. Castillo, M. Bosbous, F. Sun and R. Shaker, “A Simple Method for Estimating Respiratory Solute Dilution in Exhaled Breath Condensates,” American Journal of Respiratory & Critical Care Medicine, Vol. 168, No. 12, 2003, pp. 1500-1505. doi:10.1164/rccm.200307-920OC
I. Horvath, Z. Lazar, N. Gyulai, M. Kollai and G. Losonczy, “Exhaled Biomarkers in Lung Cancer,” European Respiratory Journal, Vol. 34, No. 1, 2009, pp. 261-275. doi:10.1183/09031936.00142508
J. Peng, J. E. Elias, C. C. Thoreen, L. J. Licklider and S. P. Gygi, “Evaluation of Multidimensional Chromatography Coupled with Tandem Mass Spectrometry (LC/LC- MS/MS) for Large-Scale Protein Analysis: The Yeast Proteome,” Journal of Proteome Research, Vol.2, No.1, 2003, pp. 43-50. doi:10.1021/pr025556v
A. S. Jackson, A. Sandrini, C. Campbell, S. Chow, P. S. Thomas and D. H. Yates, “Comparison of Biomarkers in Exhaled Breath Condensate and Bronchoalveolar Lavage,” American Journal of Respiratory Critical Care Medicine, Vol. 175, No. 3, 2007, pp. 222-227. doi:10.1164/rccm.200601-107OC
E. Gianazza, L. Allegra, E. Bucchioni, I. Eberini, L. Puglisi, F. Blasi, C. Terzano, R. Wait and C. R. Sirtori, “Increased Keratin Content Detected by Proteomic Analysis of Exhaled Breath Condensate from Healthy Persons Who Smoke,” American Journal of Medicine, Vol. 117, No. 1, 2004, pp. 51-54.
C. Gessner, H. Dihazi, S. Brettschneider, S. Hammerschmidt, H. Kuhn, K. Eschrich, T. Keller, L. Engelmann, U. Sack and H. Wirtz, “Presence of Cytokeratins in Exhaled Breath Condensate of Mechanical Ventilated Patients,” Respiratory Medicine, Vol. 102, No. 2, 2008, pp. 299-306. doi:10.1016/j.rmed.2007.08.012
H. J. Hoffmann, L. M. Tabaksblat, J. J. Enghild and R. Dahl, “Human Skin Keratins are the Major Proteins in Exhaled Breath Condensate,” European Respiratory Journal, Vol. 31, No. 2, 2008, pp. 380-384.
R. H. Wetzels, H. E. Schaafsma, I. M. Leigh, E. B. Lane, S. M. Troyanovsky, S. S. Wagenaar, G. P. Vooijs and F. C. Ramaekers, “Laminin and Type VII Collagen Distribution in Different Types of Human Lung Carcinoma: Correlation with Expression of Keratins 14, 16, 17 and 18,” Histopathology, Vol. 20, No. 4, 1992, pp. 295-303.