Discovery of distinct protein profiles specific for lung tumors and pre-malignant lung lesions by SELDI mass spectrometry

Objectives: Early lung cancer detection and treatment remain a challenge. The efficacy of surface-enhanced laser desorption/ionization (SELDI) technology in lung cancer detection, has not been defined. This study identifies specific protein peak patterns in malignant lung tumors, and in pre-malignant airways epithelium showing neoplastic transformation. Methods: Lung tumor specimens taken from patients participating in a lung cancer screening study (H. Lee Moffitt Cancer Center, Tampa, FL) were laser capture microdissected to obtain pure cell populations from frozen sections of normal lung, atypical adenomatous hyperplasia (AAH) and malignant tumors. SELDI mass spectrometry was used to generate protein profiles in each epithelial cell type. Results: SELDI mass spectroscopy is highly reproducible in detecting lung tumor-specific protein profiles. Three peaks at 17–23 kDa mass range from tumor cells showed markedly increased compared with normal cells. The peak at 17 250 Da was not detected in any of the normal cells. This peak appeared to be present at low levels in the atypical cell samples. Conclusions: This study demonstrates the feasibility of detecting “malignant” protein signatures from lung tumor and pre-malignant pulmonary epithelium using SELDI mass spectrometry. Although additional study is necessary to validate these patterns as unique diagnostic tools, these “malignant” protein signatures lend themselves to identification of populations at high-risk for lung cancer and for monitoring response to lung cancer chemopreventive agents.