PURPOSE: There is increasing evidence that altered microRNA expression is associated with tumor progression and survival in cancer patients. We tested if the expression of specific microRNAs was associated with prognosis and disease progression in early-stage lung adenocarcinoma. EXPERIMENTAL DESIGN: The expression of miR-21, miR-17, and miR-155 was measured by quantitative RT-PCR in tissues from 317 non-small cell lung cancer (NSCLC) patients that originated from Maryland, Norway, and Japan. Kaplan-Meier and Cox regression analysis evaluated associations of microRNA expression with cancer-specific mortality and disease-free survival. RESULTS: Elevated miR-21 (HR 2.06, 1.13-3.75), miR-17 (HR 2.00, 1.10-3.61), and miR-155 (HR 2.37, 1.27-4.42) was associated with worse cancer-specific mortality in the Maryland cohort. These were evaluated in two additional cohorts and only miR-21 was associated with worse cancer-specific mortality in the Norwegian cohort (HR 2.78, 1.22-6.31) and worse relapse-free survival in the Japanese cohort (HR 2.82, 1.57-5.07). More advanced stage tumors expressed significantly higher levels of miR-21 compared with TNM stage I tumors. TNM stage I patients were evaluated separately and high levels of miR-21 was associated with worse cancer-specific mortality (HR 2.16, 1.11-4.21) and relapse-free survival (3.40, 1.57-7.36) independent of other clinical factors. CONCLUSIONS: This is the first study to report that increased miR-21 expression is associated with disease progression and survival in stage I lung cancer. This suggests that expression of miR-21 may contribute to lung carcinogenesis and serve as a therapeutic target or early-stage prognostic biomarker for lung adenocarcinoma.
PURPOSE: There is increasing evidence that altered microRNA expression is associated with tumor progression and survival in cancerpatients. We tested if the expression of specific microRNAs was associated with prognosis and disease progression in early-stage lung adenocarcinoma. EXPERIMENTAL DESIGN: The expression of miR-21, miR-17, and miR-155 was measured by quantitative RT-PCR in tissues from 317 non-small cell lung cancer (NSCLC) patients that originated from Maryland, Norway, and Japan. Kaplan-Meier and Cox regression analysis evaluated associations of microRNA expression with cancer-specific mortality and disease-free survival. RESULTS: Elevated miR-21 (HR 2.06, 1.13-3.75), miR-17 (HR 2.00, 1.10-3.61), and miR-155 (HR 2.37, 1.27-4.42) was associated with worse cancer-specific mortality in the Maryland cohort. These were evaluated in two additional cohorts and only miR-21 was associated with worse cancer-specific mortality in the Norwegian cohort (HR 2.78, 1.22-6.31) and worse relapse-free survival in the Japanese cohort (HR 2.82, 1.57-5.07). More advanced stage tumors expressed significantly higher levels of miR-21 compared with TNM stage I tumors. TNM stage I patients were evaluated separately and high levels of miR-21 was associated with worse cancer-specific mortality (HR 2.16, 1.11-4.21) and relapse-free survival (3.40, 1.57-7.36) independent of other clinical factors. CONCLUSIONS: This is the first study to report that increased miR-21 expression is associated with disease progression and survival in stage I lung cancer. This suggests that expression of miR-21 may contribute to lung carcinogenesis and serve as a therapeutic target or early-stage prognostic biomarker for lung adenocarcinoma.
Authors: Ewy A Mathé; Giang Huong Nguyen; Elise D Bowman; Yiqiang Zhao; Anuradha Budhu; Aaron J Schetter; Rosemary Braun; Mark Reimers; Kensuke Kumamoto; Duncan Hughes; Nasser K Altorki; Alan G Casson; Chang-Gong Liu; Xin Wei Wang; Nozomu Yanaihara; Nobutoshi Hagiwara; Andrew J Dannenberg; Masao Miyashita; Carlo M Croce; Curtis C Harris Journal: Clin Cancer Res Date: 2009-09-29 Impact factor: 12.531
Authors: Maria Teresa Landi; Yingdong Zhao; Melissa Rotunno; Jill Koshiol; Hui Liu; Andrew W Bergen; Maurizia Rubagotti; Alisa M Goldstein; Ilona Linnoila; Francesco M Marincola; Margaret A Tucker; Pier Alberto Bertazzi; Angela C Pesatori; Neil E Caporaso; Lisa M McShane; Ena Wang Journal: Clin Cancer Res Date: 2010-01-12 Impact factor: 12.531
Authors: Hirokazu Okayama; Motonobu Saito; Naohide Oue; Jonathan M Weiss; Jimmy Stauffer; Seiichi Takenoshita; Robert H Wiltrout; S Perwez Hussain; Curtis C Harris Journal: Int J Cancer Date: 2012-06-13 Impact factor: 7.396