A panel of sputum-based genomic marker for early detection of lung cancer.
Non-small cell lung cancer (NSCLC) is the leading cause of cancer death. Early detection of NSCLC will improve its outcome. We previously identified genetic signatures whose genomic copy number aberrations were associated with early stage NSCLC. Here, we aimed to develop a panel of genes that could be detected in sputum for NSCLC early detection. We first optimized a panel of genes by using an in situ minichip for measuring changes of the signatures in sputum of a case-control cohort of 49 NSCLC patients, 49 patients with chronic obstructive pulmonary disease (COPD), and 49 healthy smokers. We then validated the genes in an independent cohort of 69 NSCLC patients and 65 noncancer subjects. The results were compared with those of sputum cytology. Fifteen genes showed significant differences of their copy number changes in sputum between NSCLC and both COPD and healthy subjects. A logistic regression model with the best prediction was built on the basis of 6 genes, ENO1, FHIT, HYAL2, SKP2, p16, and 14-3-3zeta. The composite of the 6 genes produced 86.7% sensitivity and 93.9% specificity in distinguishing stage I NSCLC patients from the noncancer individuals. Furthermore, the genes had higher sensitivity (86.9%) in identification of squamous cell carcinoma (SCC) than in adenocarcinoma of the lungs (80.8%; P < 0.05). Validation of the genes in the independent cohort confirmed their diagnostic power that also showed higher accuracy for lung SCCs than for sputum cytology. The gene panel could provide sputum-based markers that have the potential to improve early detection of lung SCCs.
Jiang
Feng
F
Department of Pathology, The University of Maryland School of Medicine, Baltimore, MD 21201, USA. fjiang@som.umaryland.edu
Todd
Nevins W
NW
Li
Ruiyun
R
Zhang
Howard
H
Fang
Hongbin
H
Stass
Sanford A
SA
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000235:genetics; D016022:Case-Control Studies; D015331:Cohort Studies; D042241:Early Diagnosis; D005260:Female; D005819:Genetic Markers / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012372:ROC Curve; D012680:Sensitivity and Specificity; D013183:Sputum / Q000378:metabolism*
D005819:Genetic Markers