PURPOSE: The definition of the malignant status of indeterminate pulmonary nodules detected by chance in CT scans is of high clinical relevance. Less invasive methods would enhance the efficiency of interventions. We investigated potential molecular biomarkers in endobronchial epithelial linig fluid (ELF) collected by bronchoscopic microsampling.
METHODS: The samples were collected from subsegmental bronchi as close to the indeterminate pulmonary nodule as technically possible, and from the contralateral lung for control purposes. Confirmation of diagnosis was achieved as usual by histopathology of the transbronchial biopsy or surgery. From the 71 patients included prospectively in the study, 51 turned out to be NSCLC, 20 were benign. The ELF samples were processed to extract RNA by standard methods, a subset of samples from 15 patients was screened for differentially expressed genes by microarray analysis. A total of 13 potential biomarkers were further introduced into qRT-PCR based validation using the independent ELF samples from 56 patients of the study population.
RESULTS: One biomarker candidate turned out to be particularly promising, since it was significantly up- regulated in ELF samples of NSCLC patients independent of the tumor subtype, when compared to the cases with benign diagnosis.
CONCLUSIONS: The predictive value of the biomarker for NSCLC diagnosis may be further enhanced by including clinical parameters like nodule size in a combined analysis.
CLINICAL IMPLICATIONS: The measurement of specific biomarkers in ELF obtained by bronchoscopic microsampling may clear the way for a powerful tool for the early and less invasive differentiation between malignant and benign pulmonary nodules.
DISCLOSURE: The following authors have nothing to disclose: Nicolas Kahn, Michael Meister, Ralf Eberhardt, Thomas Muley, Philipp Schnabel, Christian Bender, Marc Johannes, Holger Sueltmann, Felix Herth, Ruprecht Kuner
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