Document Detail


Airway epithelial gene expression in the diagnostic evaluation of smokers with suspect lung cancer.
MedLine Citation:
PMID:  17334370     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
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
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Validation Studies     Date:  2007-03-04
Journal Detail:
Title:  Nature medicine     Volume:  13     ISSN:  1078-8956     ISO Abbreviation:  Nat. Med.     Publication Date:  2007 Mar 
Date Detail:
Created Date:  2007-03-07     Completed Date:  2007-05-10     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  9502015     Medline TA:  Nat Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  361-6     Citation Subset:  IM    
Affiliation:
The Pulmonary Center, Boston University Medical Center, 715 Albany Street, Boston, Massachusetts 02118, USA. aspira@bu.edu
Data Bank Information
Bank Name/Acc. No.:
GEO/GSE4115
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MeSH Terms
Descriptor/Qualifier:
Biological Markers / metabolism
Gene Expression Profiling*
Gene Expression Regulation, Neoplastic*
Humans
Lung Neoplasms / diagnosis*,  metabolism,  pathology
Oligonucleotide Array Sequence Analysis
Prospective Studies
Respiratory Mucosa / metabolism*,  pathology
Smoking / adverse effects*,  genetics
Tumor Markers, Biological
Grant Support
ID/Acronym/Agency:
ES10377/ES/NIEHS NIH HHS; R21CA10650/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Tumor Markers, Biological

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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