Airway epithelial gene expression in the diagnostic evaluation of smokers with suspect lung cancer
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
HERO ID
2473970
Reference Type
Journal Article
Year
2007
Language
English
PMID
| HERO ID | 2473970 |
|---|---|
| In Press | No |
| Year | 2007 |
| Title | Airway epithelial gene expression in the diagnostic evaluation of smokers with suspect lung cancer |
| 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 |
| Journal | Nature Medicine |
| Volume | 13 |
| Issue | 3 |
| Page Numbers | 361-366 |
| 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. |
| Doi | 10.1038/nm1556 |
| Pmid | 17334370 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |