Airway epithelial gene expression in the diagnostic evaluation of smokers with suspect lung cancer.
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.
Spira
Avrum
A
The Pulmonary Center, Boston University Medical Center, 715 Albany Street, Boston, Massachusetts 02118, USA. aspira@bu.edu
Beane
Jennifer E
JE
Shah
Vishal
V
Steiling
Katrina
K
Liu
Gang
G
Schembri
Frank
F
Gilman
Sean
S
Dumas
Yves-Martine
YM
Calner
Paul
P
Sebastiani
Paola
P
Sridhar
Sriram
S
Beamis
John
J
Lamb
Carla
C
Anderson
Timothy
T
Gerry
Norman
N
Keane
Joseph
J
Lenburg
Marc E
ME
Brody
Jerome S
JS
D015415:Biomarkers / Q000378:metabolism; D014408:Biomarkers, Tumor; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D011446:Prospective Studies; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000473:pathology; D012907:Smoking / Q000009:adverse effects* / Q000235:genetics
D015415:Biomarkers; D014408:Biomarkers, Tumor