Airway epithelial gene expression in the diagnostic evaluation of smokers with suspect lung cancer.

Authors:	Avrum Spira, Jennifer E Beane, Vishal Shah, Katrina Steiling, Gang Liu, Frank Schembri, Sean Gilman, Yves-Martine Dumas, Paul Calner, Paola Sebastiani, Sriram Sridhar, John Beamis, Carla Lamb, Timothy Anderson, Norman Gerry, Joseph Keane, Marc E Lenburg, Jerome S Brody
Language:	Eng.
Date:	2007-03-07
Journal:	Nature medicine (1078-8956)
Release:	Nat Med. 2007 Mar;13(3):361-6
Abstract:	Lung cancer is the leading cause of death from cancer in the US and the world. The high mortality rate (80-85% within 5 years) results, in part, from a lack of effective tools to diagnose the disease at an early stage. Given that cigarette smoke creates a field of injury throughout the airway, we sought to determine if gene expression in histologically normal large-airway epithelial cells obtained at bronchoscopy from smokers with suspicion of lung cancer could be used as a lung cancer biomarker. Using a training set (n = 77) and gene-expression profiles from Affymetrix HG-U133A microarrays, we identified an 80-gene biomarker that distinguishes smokers with and without lung cancer. We tested the biomarker on an independent test set (n = 52), with an accuracy of 83% (80% sensitive, 84% specific), and on an additional validation set independently obtained from five medical centers (n = 35). Our biomarker had approximately 90% sensitivity for stage 1 cancer across all subjects. Combining cytopathology of lower airway cells obtained at bronchoscopy with the biomarker yielded 95% sensitivity and a 95% negative predictive value. These findings indicate that gene expression in cytologically normal large-airway epithelial cells can serve as a lung cancer biomarker, potentially owing to a cancer-specific airway-wide response to cigarette smoke.
Copyright:	Nature medicine The Pulmonary Center, Boston University Medical Center, 715 Albany Street, Boston, Massachusetts 02118, USA. aspira bu.edu
Full text:	DOI - Nature medicine (DOI) EBSCO - HTML (needs subscription) Nature Publishing Group - HTML (needs subscription) ProQuest Information and Learning - HTML (needs subscription) Swets Information Services - HTML (needs subscription)
Terms:	Biological Markers, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Lung Neoplasms, Oligonucleotide Array Sequence Analysis, Prospective Studies, Respiratory Mucosa, Smoking, Tumor Markers, Biological