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

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.

journal_name

Nat Med

journal_title

Nature medicine

authors

Spira A,Beane JE,Shah V,Steiling K,Liu G,Schembri F,Gilman S,Dumas YM,Calner P,Sebastiani P,Sridhar S,Beamis J,Lamb C,Anderson T,Gerry N,Keane J,Lenburg ME,Brody JS

doi

10.1038/nm1556

subject

Has Abstract

pub_date

2007-03-01 00:00:00

pages

361-6

issue

3

eissn

1078-8956

issn

1546-170X

pii

nm1556

journal_volume

13

pub_type

杂志文章

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