Diagnostic for lung disorders using class prediction
The present invention provides methods for diagnosis and prognosis of lung cancer using expression analysis of one or more groups of genes, and a combination of expression analysis with bronchoscopy. The methods of the invention provide far superior detection accuracy for lung cancer when compared to any other currently available method for lung cancer diagnostic or prognosis. The invention also provides methods of diagnosis and prognosis of other lung diseases, particularly in individuals who are exposed to air pollutants, such as cigarette or cigar smoke, smog, asbestos and the like air contaminants or pollutants.
1. A method of processing a sample of histologically normal airway epithelial cells from a bronchus or buccal mucosa of a subject being screened for lung cancer, comprising:
(a) receiving the sample of histologically normal airway epithelial cells from the bronchus or buccal mucosa of the subject being screened for lung cancer; and
(b) measuring an expression level of at least AKR1C2 in the sample, by reverse-transcription polymerase chain reaction (RT-PCR) analysis, nucleic acid chip analysis, or messenger RNA analysis, wherein transcripts of at least 10 and no more than 50 genes are measured.
2. The method of claim 1 , wherein (b) comprises measuring the expression level of at least AKR1C2 by messenger RNA analysis.
3. The method of claim 1 , wherein (b) comprises measuring transcripts of at least 20 genes.
4. The method of claim 1 , wherein the airway epithelial cells are from the bronchus.
5. The method of claim 1 , wherein the airway epithelial cells are not from the bronchus.
6. The method of claim 1 , wherein the subject has been exposed to air pollution.
7. The method of claim 1 , wherein the subject is a smoker.
8. The method of claim 1 , wherein the subject is a former smoker.
9. The method of claim 1 , wherein the subject has been exposed to asbestos.
10. The method of claim 1 , wherein the subject has undergone a bronchoscopy.
11. The method of claim 1 , wherein the subject is suspected of having lung cancer.
12. The method of claim 1 , wherein (b) comprises measuring the expression level of at least AKR1C2 by an assay selected from the group consisting of RNA quantification using PCR and complementary DNA (cDNA) arrays; real competitive PCR using MALDI-TOF Mass spectrometry; solid-phase mini-sequencing based upon a primer extension reaction; ion-pair high-performance liquid chromatography; and real-time RT-PCR.