PURPOSE: Clinical staging does not adequately risk stratify patients with early stage non-small cell lung cancer. We sought to generate a real-time PCR (RT-PCR)-based prognostic model in patients with early stage lung adenocarcinoma, the dominant histology of lung cancer in the United States. EXPERIMENTAL DESIGN: We studied gene expression of 61 candidate genes in 107 patients with completely surgically resected lung adenocarcinoma using RT-PCR. We used crossvalidation methods to select and validate a prognostic model based on the expression of a limited number of genes. A risk score was generated based on model coefficients, and survival of patients with high- and low-risk scores were analyzed. RESULTS: We generated a four-gene model based on expression of WNT3a, ERBB3, LCK, and RND3. Risk score predicted mortality better than clinical stage or tumor size (adjusted hazard ratio, 6.7; 95% confidence interval, 1.6-28.9; P=0.001). Among 70 patients with stage I disease, 5-year overall survival was 87% among patients with low-risk scores, and 38% among patients with high-risk scores (P=0.0002). Among all patients, 5-year overall survival was 62% and 41%, respectively (P=0.0054). Disease-free survival was also significantly different among low- and high-risk score patients. CONCLUSIONS: This multigene assay predicts overall and disease-free survival significantly better than clinical stage and tumor size in patients with early stage lung adenocarcinoma and performs especially well in patients with stage I disease. Prospective clinical trials are needed to determine whether high-risk patients with stage I disease benefit from adjuvant chemotherapy.
PURPOSE: Clinical staging does not adequately risk stratify patients with early stage non-small cell lung cancer. We sought to generate a real-time PCR (RT-PCR)-based prognostic model in patients with early stage lung adenocarcinoma, the dominant histology of lung cancer in the United States. EXPERIMENTAL DESIGN: We studied gene expression of 61 candidate genes in 107 patients with completely surgically resected lung adenocarcinoma using RT-PCR. We used crossvalidation methods to select and validate a prognostic model based on the expression of a limited number of genes. A risk score was generated based on model coefficients, and survival of patients with high- and low-risk scores were analyzed. RESULTS: We generated a four-gene model based on expression of WNT3a, ERBB3, LCK, and RND3. Risk score predicted mortality better than clinical stage or tumor size (adjusted hazard ratio, 6.7; 95% confidence interval, 1.6-28.9; P=0.001). Among 70 patients with stage I disease, 5-year overall survival was 87% among patients with low-risk scores, and 38% among patients with high-risk scores (P=0.0002). Among all patients, 5-year overall survival was 62% and 41%, respectively (P=0.0054). Disease-free survival was also significantly different among low- and high-risk score patients. CONCLUSIONS: This multigene assay predicts overall and disease-free survival significantly better than clinical stage and tumor size in patients with early stage lung adenocarcinoma and performs especially well in patients with stage I disease. Prospective clinical trials are needed to determine whether high-risk patients with stage I disease benefit from adjuvant chemotherapy.
Authors: Dung-Tsa Chen; Ying-Lin Hsu; William J Fulp; Domenico Coppola; Eric B Haura; Timothy J Yeatman; W Douglas Cress Journal: J Natl Cancer Inst Date: 2011-12-08 Impact factor: 13.506
Authors: Johannes R Kratz; Jianxing He; Stephen K Van Den Eeden; Zhi-Hua Zhu; Wen Gao; Patrick T Pham; Michael S Mulvihill; Fatemeh Ziaei; Huanrong Zhang; Bo Su; Xiuyi Zhi; Charles P Quesenberry; Laurel A Habel; Qiuhua Deng; Zongfei Wang; Jiangfen Zhou; Huiling Li; Mei-Chun Huang; Che-Chung Yeh; Mark R Segal; M Roshni Ray; Kirk D Jones; Dan J Raz; Zhidong Xu; Thierry M Jahan; David Berryman; Biao He; Michael J Mann; David M Jablons Journal: Lancet Date: 2012-01-27 Impact factor: 79.321
Authors: Junichi Okamoto; Johannes R Kratz; Tomomi Hirata; Iwao Mikami; Dan Raz; Mark Segal; Zhao Chen; Hai-Meng Zhou; Patrick Pham; Hui Li; Adam Yagui-Beltran; Adam Beltran; M Roshni Ray; Kiyoshi Koizumi; Kazuo Shimizu; David Jablons; Biao He Journal: Clin Lung Cancer Date: 2011-04-24 Impact factor: 4.785