Background Current staging methods are inadequate for predictingthe outcome of treatment of nonsmall-cell lung cancer(NSCLC). We developed a five-gene signature that is closelyassociated with survival of patients with NSCLC.
Methods We used computer-generated random numbers to assign185 frozen specimens for microarray analysis, real-time reverse-transcriptasepolymerase chain reaction (RT-PCR) analysis, or both. We studiedgene expression in frozen specimens of lung-cancer tissue from125 randomly selected patients who had undergone surgical resectionof NSCLC and evaluated the association between the level ofexpression and survival. We used risk scores and decision-treeanalysis to develop a gene-expression model for the predictionof the outcome of treatment of NSCLC. For validation, we usedrandomly assigned specimens from 60 other patients.
Results Sixteen genes that correlated with survival among patientswith NSCLC were identified by analyzing microarray data andrisk scores. We selected five genes (DUSP6, MMD, STAT1, ERBB3,and LCK) for RT-PCR and decision-tree analysis. The five-genesignature was an independent predictor of relapse-free and overallsurvival. We validated the model with data from an independentcohort of 60 patients with NSCLC and with a set of publishedmicroarray data from 86 patients with NSCLC.
Conclusions Our five-gene signature is closely associated withrelapse-free and overall survival among patients with NSCLC.
Source Information
From National Taiwan University College of Public Health (H.-Y.C., W.J.C.), National Taiwan University College of Medicine (H.-Y.C., S.-L.Y., C.-L.C., C.-H.W., S.-F.K., H.-N.L., S.S., W.J.C., J.J.W.C., P.-C.Y.), Academia Sinica (C.-H.C, P.-C.Y.), National Taiwan University Hospital (A.Y., W.-K.C., P.-C.Y.), and Advpharma (H.-J.T.) all in Taipei, Taiwan; and Taichung Veterans General Hospital (G.-C.C., C.-Y.C.) and National Chung-Hsing University (G.-C.C., C.-C.L., J.J.W.C.) both in Taichung, Taiwan. Drs. W.J. Chen, J.J.W. Chen, and P.C. Yang contributed equally to this article.
Address reprint requests to Dr. Yang at the Department of Internal Medicine, National Taiwan University Hospital, No. 7, Chung-Shan S. Rd., Taipei, Taiwan 100, or at pcyang{at}ha.mc.ntu.edu.tw.
Five-Gene Signature in NonSmall-Cell Lung Cancer
Michiels S., Hill C., Raz D. J., Jablons D. M., Dobbin K. K., Gounaris I., Quintás-Cardama A., Gibbons D. L., Chen H.-Y., Chen W. J., Yang P.-C.
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N Engl J Med 2007;
356:1581-1583, Apr 12, 2007.
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