Background Current staging methods are inadequate for predictingthe outcome of treatment of non–small-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 Non–Small-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.
Extract |
Full Text |
PDF
N Engl J Med 2007;
356:1581-1583, Apr 12, 2007.
Correspondence
This article has been cited by other articles:
Okudela, K., Yazawa, T., Woo, T., Sakaeda, M., Ishii, J., Mitsui, H., Shimoyamada, H., Sato, H., Tajiri, M., Ogawa, N., Masuda, M., Takahashi, T., Sugimura, H., Kitamura, H.
(2009). Down-Regulation of DUSP6 Expression in Lung Cancer: Its Mechanism and Potential Role in Carcinogenesis. Am. J. Pathol.
175: 867-881
[Abstract][Full Text]
Raponi, M., Dossey, L., Jatkoe, T., Wu, X., Chen, G., Fan, H., Beer, D. G.
(2009). MicroRNA Classifiers for Predicting Prognosis of Squamous Cell Lung Cancer. Cancer Res.
69: 5776-5783
[Abstract][Full Text]
Colice, G.
(2009). Lung Cancer Staging and the Home Insurance Building Constructed in 1884-1885. Chest
136: 6-8
[Full Text]
Tomida, S., Takeuchi, T., Shimada, Y., Arima, C., Matsuo, K., Mitsudomi, T., Yatabe, Y., Takahashi, T.
(2009). Relapse-Related Molecular Signature in Lung Adenocarcinomas Identifies Patients With Dismal Prognosis. JCO
27: 2793-2799
[Abstract][Full Text]
Huang, Y.-T., Heist, R. S., Chirieac, L. R., Lin, X., Skaug, V., Zienolddiny, S., Haugen, A., Wu, M. C., Wang, Z., Su, L., Asomaning, K., Christiani, D. C.
(2009). Genome-Wide Analysis of Survival in Early-Stage Non-Small-Cell Lung Cancer. JCO
27: 2660-2667
[Abstract][Full Text]
Dubey, S., Powell, C. A.
(2009). Update in Lung Cancer 2008. Am. J. Respir. Crit. Care Med.
179: 860-868
[Full Text]
Gordon, G. J., Dong, L., Yeap, B. Y., Richards, W. G., Glickman, J. N., Edenfield, H., Mani, M., Colquitt, R., Maulik, G., Van Oss, B., Sugarbaker, D. J., Bueno, R.
(2009). Four-Gene Expression Ratio Test for Survival in Patients Undergoing Surgery for Mesothelioma. JNCI J Natl Cancer Inst
101: 678-686
[Abstract][Full Text]
Ebi, H., Tomida, S., Takeuchi, T., Arima, C., Sato, T., Mitsudomi, T., Yatabe, Y., Osada, H., Takahashi, T.
(2009). Relationship of Deregulated Signaling Converging onto mTOR with Prognosis and Classification of Lung Adenocarcinoma Shown by Two Independent In silico Analyses. Cancer Res.
69: 4027-4035
[Abstract][Full Text]
Borczuk, A. C., Toonkel, R. L., Powell, C. A.
(2009). Genomics of Lung Cancer. Proc Am Thorac Soc
6: 152-158
[Abstract][Full Text]
Kashani-Sabet, M., Rangel, J., Torabian, S., Nosrati, M., Simko, J., Jablons, D. M., Moore, D. H., Haqq, C., Miller, J. R. III, Sagebiel, R. W.
(2009). A multi-marker assay to distinguish malignant melanomas from benign nevi. Proc. Natl. Acad. Sci. USA
106: 6268-6272
[Abstract][Full Text]
Haas, A. R.
(2009). Infectious complications from full extension endobronchial ultrasound transbronchial needle aspiration. Eur Respir J
33: 935-938
[Abstract][Full Text]
Pennell, N. A., Lynch, T. J. Jr.
(2009). Combined Inhibition of the VEGFR and EGFR Signaling Pathways in the Treatment of NSCLC. The Oncologist
14: 399-411
[Abstract][Full Text]
de Reynies, A., Assie, G., Rickman, D. S., Tissier, F., Groussin, L., Rene-Corail, F., Dousset, B., Bertagna, X., Clauser, E., Bertherat, J.
(2009). Gene Expression Profiling Reveals a New Classification of Adrenocortical Tumors and Identifies Molecular Predictors of Malignancy and Survival. JCO
27: 1108-1115
[Abstract][Full Text]
Zhu, Z.-H., Sun, B.-Y., Ma, Y., Shao, J.-Y., Long, H., Zhang, X., Fu, J.-H., Zhang, L.-J., Su, X.-D., Wu, Q.-L., Ling, P., Chen, M., Xie, Z.-M., Hu, Y., Rong, T.-H.
(2009). Three Immunomarker Support Vector Machines-Based Prognostic Classifiers for Stage IB Non-Small-Cell Lung Cancer. JCO
27: 1091-1099
[Abstract][Full Text]
Grinberg-Rashi, H., Ofek, E., Perelman, M., Skarda, J., Yaron, P., Hajduch, M., Jacob-Hirsch, J., Amariglio, N., Krupsky, M., Simansky, D. A., Ram, Z., Pfeffer, R., Galernter, I., Steinberg, D. M., Ben-Dov, I., Rechavi, G., Izraeli, S.
(2009). The Expression of Three Genes in Primary Non-Small Cell Lung Cancer Is Associated with Metastatic Spread to the Brain. Clin. Cancer Res.
15: 1755-1761
[Abstract][Full Text]
Boutros, P. C., Lau, S. K., Pintilie, M., Liu, N., Shepherd, F. A., Der, S. D., Tsao, M.-S., Penn, L. Z., Jurisica, I.
(2009). Prognostic gene signatures for non-small-cell lung cancer. Proc. Natl. Acad. Sci. USA
106: 2824-2828
[Abstract][Full Text]
Broet, P., Camilleri-Broet, S., Zhang, S., Alifano, M., Bangarusamy, D., Battistella, M., Wu, Y., Tuefferd, M., Regnard, J.-F., Lim, E., Tan, P., Miller, L. D.
(2009). Prediction of Clinical Outcome in Multiple Lung Cancer Cohorts by Integrative Genomics: Implications for Chemotherapy Selection. Cancer Res.
69: 1055-1062
[Abstract][Full Text]
Roepman, P., Jassem, J., Smit, E. F., Muley, T., Niklinski, J., van de Velde, T., Witteveen, A. T., Rzyman, W., Floore, A., Burgers, S., Giaccone, G., Meister, M., Dienemann, H., Skrzypski, M., Kozlowski, M., Mooi, W. J., van Zandwijk, N.
(2009). An Immune Response Enriched 72-Gene Prognostic Profile for Early-Stage Non-Small-Cell Lung Cancer. Clin. Cancer Res.
15: 284-290
[Abstract][Full Text]
Guo, N. L., Wan, Y.-W., Tosun, K., Lin, H., Msiska, Z., Flynn, D. C., Remick, S. C., Vallyathan, V., Dowlati, A., Shi, X., Castranova, V., Beer, D. G., Qian, Y.
(2008). Confirmation of Gene Expression-Based Prediction of Survival in Non-Small Cell Lung Cancer. Clin. Cancer Res.
14: 8213-8220
[Abstract][Full Text]
Lee, E.-S., Son, D.-S., Kim, S.-H., Lee, J., Jo, J., Han, J., Kim, H., Lee, H. J., Choi, H. Y., Jung, Y., Park, M., Lim, Y. S., Kim, K., Shim, Y. M., Kim, B. C., Lee, K., Huh, N., Ko, C., Park, K., Lee, J. W., Choi, Y. S., Kim, J.
(2008). Prediction of Recurrence-Free Survival in Postoperative Non-Small Cell Lung Cancer Patients by Using an Integrated Model of Clinical Information and Gene Expression. Clin. Cancer Res.
14: 7397-7404
[Abstract][Full Text]
Xi, L., Feber, A., Gupta, V., Wu, M., Bergemann, A. D., Landreneau, R. J., Litle, V. R., Pennathur, A., Luketich, J. D., Godfrey, T. E.
(2008). Whole genome exon arrays identify differential expression of alternatively spliced, cancer-related genes in lung cancer. Nucleic Acids Res
36: 6535-6547
[Abstract][Full Text]
Herbst, R. S., Heymach, J. V., Lippman, S. M.
(2008). Lung Cancer. NEJM
359: 1367-1380
[Full Text]
Raz, D. J., Ray, M. R., Kim, J. Y., He, B., Taron, M., Skrzypski, M., Segal, M., Gandara, D. R., Rosell, R., Jablons, D. M.
(2008). A Multigene Assay Is Prognostic of Survival in Patients with Early-Stage Lung Adenocarcinoma. Clin. Cancer Res.
14: 5565-5570
[Abstract][Full Text]
Skrzypski, M., Jassem, E., Taron, M., Sanchez, J. J., Mendez, P., Rzyman, W., Gulida, G., Raz, D., Jablons, D., Provencio, M., Massuti, B., Chaib, I., Perez-Roca, L., Jassem, J., Rosell, R.
(2008). Three-Gene Expression Signature Predicts Survival in Early-Stage Squamous Cell Carcinoma of the Lung. Clin. Cancer Res.
14: 4794-4799
[Abstract][Full Text]
Herth, F. J.F., Morgan, R. K., Eberhardt, R., Ernst, A.
(2008). Endobronchial Ultrasound-Guided Miniforceps Biopsy in the Biopsy of Subcarinal Masses in Patients with Low Likelihood of Non-Small Cell Lung Cancer. Ann. Thorac. Surg.
85: 1874-1878
[Abstract][Full Text]
Kim, S.-O., Jeong, J.-Y., Kim, M.-R., Cho, H.-J., Ju, J.-Y., Kwon, Y.-S., Oh, I.-J., Kim, K.-S., Kim, Y.-I., Lim, S.-C., Kim, Y.-C.
(2008). Efficacy of Gemcitabine in Patients with Non-Small Cell Lung Cancer According to Promoter Polymorphisms of the Ribonucleotide Reductase M1 Gene. Clin. Cancer Res.
14: 3083-3088
[Abstract][Full Text]
Dubey, S., Powell, C. A.
(2008). Update in Lung Cancer 2007. Am. J. Respir. Crit. Care Med.
177: 941-946
[Full Text]
Sugimura, H.
(2008). Detection of chromosome changes in pathology archives: an application of microwave-assisted fluorescence in situ hybridization to human carcinogenesis studies. Carcinogenesis
29: 681-687
[Abstract][Full Text]
Reed, C. E., Graham, A., Hoda, R. S., Khoor, A., Garrett-Mayer, E., Wallace, M. B., Mitas, M.
(2008). A simple two-gene prognostic model for adenocarcinoma of the lung. J. Thorac. Cardiovasc. Surg.
135: 627-634
[Abstract][Full Text]
Ost, D., Goldberg, J., Rolnitzky, L., Rom, W. N.
(2008). Survival after Surgery in Stage IA and IB Non-Small Cell Lung Cancer. Am. J. Respir. Crit. Care Med.
177: 516-523
[Abstract][Full Text]
Haasbeek, C. J.A., Senan, S., Smit, E. F., Paul, M. A., Slotman, B. J., Lagerwaard, F. J.
(2008). Critical Review of Nonsurgical Treatment Options for Stage I Non-Small Cell Lung Cancer. The Oncologist
13: 309-319
[Abstract][Full Text]
Sun, Z., Wigle, D. A., Yang, P.
(2008). Non-Overlapping and Non-Cell-Type-Specific Gene Expression Signatures Predict Lung Cancer Survival. JCO
26: 877-883
[Abstract][Full Text]
Bradbury, P. A., Heist, R. S., Kulke, M. H., Zhou, W., Marshall, A. L., Miller, D. P., Su, L., Park, S., Temel, J., Fidias, P., Sequist, L., Lynch, T. J., Wain, J. C., Shepherd, F. A., Christiani, D. C., Liu, G.
(2008). A Rapid Outcomes Ascertainment System Improves the Quality of Prognostic and Pharmacogenetic Outcomes from Observational Studies. Cancer Epidemiol. Biomarkers Prev.
17: 204-211
[Abstract][Full Text]
Stearman, R. S., Dwyer-Nield, L., Grady, M. C., Malkinson, A. M., Geraci, M. W.
(2008). A Macrophage Gene Expression Signature Defines a Field Effect in the Lung Tumor Microenvironment. Cancer Res.
68: 34-43
[Abstract][Full Text]
Lau, S. K., Boutros, P. C., Pintilie, M., Blackhall, F. H., Zhu, C.-Q., Strumpf, D., Johnston, M. R., Darling, G., Keshavjee, S., Waddell, T. K., Liu, N., Lau, D., Penn, L. Z., Shepherd, F. A., Jurisica, I., Der, S. D., Tsao, M.-S.
(2007). Three-Gene Prognostic Classifier for Early-Stage Non Small-Cell Lung Cancer. JCO
25: 5562-5569
[Abstract][Full Text]
Timmons, B. C., Mahendroo, M.
(2007). Processes Regulating Cervical Ripening Differ From Cervical Dilation and Postpartum Repair: Insights From Gene Expression Studies. Reproductive Sciences
14: 53-62
[Abstract]
Tino, G.
(2007). Clinical Year in Review I: Lung Cancer, Interventional Pulmonology, Pediatric Pulmonary Disease, and Pulmonary Vascular Disease. Proc Am Thorac Soc
4: 478-481
[Full Text]
Schwartz, A. M., Henson, D. E.
(2007). Diagnostic Surgical Pathology in Lung Cancer: ACCP Evidence-Based Clinical Practice Guidelines (2nd Edition). Chest
132: 78S-93S
[Abstract][Full Text]
Janes, S. M., McCaughan, F.
(2007). Where next for lung cancer gene expression profiling?. Eur Respir J
30: 5-6
[Full Text]
Haussmann, H.-J.
(2007). Smoking and Lung Cancer: Future Research Directions. International Journal of Toxicology
26: 353-364
[Abstract][Full Text]
Angeloni, D.
(2007). Molecular analysis of deletions in human chromosome 3p21 and the role of resident cancer genes in disease. Brief Funct Genomic Proteomic
0: elm007v1-21
[Abstract][Full Text]
Michiels, S., Hill, C., Raz, D. J., Jablons, D. M., Dobbin, K. K., Gounaris, I., Quintas-Cardama, A., Gibbons, D. L., Chen, H.-Y., Chen, W. J., Yang, P.-C.
(2007). Five-Gene Signature in Non-Small-Cell Lung Cancer. NEJM
356: 1581-1583
[Full Text]
Caporaso, N. E.
(2007). Integrative Study Designs--Next Step in the Evolution of Molecular Epidemiology?. Cancer Epidemiol. Biomarkers Prev.
16: 365-366
[Full Text]
(2007). Five-Gene Signature for Survival in Non-Small-Cell Lung Cancer Patients. JWatch Oncology and Hematology
2007: 1-1
[Full Text]
Herbst, R. S., Lippman, S. M.
(2007). Molecular Signatures of Lung Cancer -- Toward Personalized Therapy. NEJM
356: 76-78
[Full Text]
Previous
