Identification of ENO1 As a Potential Sputum Biomarker for Early-Stage Lung Cancer by Shotgun Proteomics

With the objective of identifying sputum biomarkers for early-stage lung cancer, we used shotgun proteomics to detect protein profiles in sputum supernatants from 6 patients with early-stage lung cancer and 5 cancer-free controls. Validating the protein profiling in additional cases and controls using western blotting and enzyme-linked immunosorbent assay (ELISA) suggested that enolase 1(ENO1) might be a potential sputum biomarker for early-stage lung cancer. Background: Lung cancer is the leading cancer killer. Early detection will reduce the related deaths. The objective of this study was to identify potential biomarkers for early-stage lung cancer in sputum supernatant. Materials and Methods: Using shotgun proteomics, we detected changes in protein profiles that were associated with lung cancer by analyzing sputum supernatants from 6 patients with early-stage lung cancer and 5 cancer-free controls. Using western blotting, we validated the proteomic results in 22 lung cancer cases and 22 controls. Using enzyme-linked immunosorbent assay (ELISA), we evaluated the diagnostic performance of the biomarker candidates in an independent set of 35 cases and 36 controls. Results: Proteomics identified 8 biomarker candidates for lung cancer. Western blotting validation of the candidates showed that enolase 1 (ENO1) displayed a higher expression level in patients with cancer than in cancer-free individuals (P = .015). ELISA revealed that the assessment of ENO1 expression in sputum supernatant had 58.33% sensitivity and 80.00% specificity in distinguishing patients with stage I lung cancer from cancer-free individuals. Conclusion: The analysis of protein biomarkers in sputum may provide a potential approach for the early detection of lung cancer. Future validation of all the candidates defined by shotgun proteomics in a large cohort study may help develop additional biomarkers that can be added to ENO1 to provide more diagnostic efficacy for lung cancer.