Lung Cancer Diagnosis from Proteomic Analysis of Preinvasive Lesions

• Published in: Cancer research (Chicago, Ill.) Vol. 71; no. 8; pp. 3009 - 3017
• Main Authors: JAMSHEDUR RAHMAN, S. M, GONZALEZ, Adriana L, PUTNAM, Joe B, MILLER, York E, FRANKLIN, Wilbur A, BLOT, William J, CARBONE, David P, SHYR, Yu, CAPRIOLI, Richard M, MASSION, Pierre P, MING LI, SEELE, Erin H, ZIMMERMAN, Lisa J, ZHANG, Xueqiong J, MANIER, M. Lisa, OLSON, Sandra J, SHAH, Ronak N, MILLER, Alison N
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.04.2011
• Subjects: Aged; Antineoplastic agents; Biological and medical sciences; Blotting, Western; Early Detection of Cancer - methods; Female; Humans; Immunohistochemistry; Lung Neoplasms - diagnosis; Lung Neoplasms - metabolism; Male; Medical sciences; Middle Aged; Neoplasm Proteins - analysis; Neoplasm Proteins - metabolism; Pharmacology. Drug treatments; Pneumology; Proteomics - methods; Reproducibility of Results; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods; Tumors; Tumors of the respiratory system and mediastinum; Lung disease; Premalignant lesion; Respiratory disease; Analysis; Lung cancer; Proteomics; Bronchus disease; Malignant tumor; Diagnosis; Bronchopulmonary; Cancer
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.can-10-2510

Early detection may help improve survival from lung cancer. In this study, our goal was to derive and validate a signature from the proteomic analysis of bronchial lesions that could predict the diagnosis of lung cancer. Using previously published studies of bronchial tissues, we selected a signature of nine matrix-assisted laser desorption ionization mass spectrometry (MALDI MS) mass-to-charge ratio features to build a prediction model diagnostic of lung cancer. The model was based on MALDI MS signal intensity (MALDI score) from bronchial tissue specimens from our 2005 published cohort of 51 patients. The performance of the prediction model in identifying lung cancer was tested in an independent cohort of bronchial specimens from 60 patients. The probability of having lung cancer based on the proteomic analysis of the bronchial specimens was characterized by an area under the receiver operating characteristic curve of 0.77 (95% CI 0.66-0.88) in this validation cohort. Eight of the nine features were identified and validated by Western blotting and immunohistochemistry. These results show that proteomic analysis of endobronchial lesions may facilitate the diagnosis of lung cancer and the monitoring of high-risk individuals for lung cancer in surveillance and chemoprevention trials.