Validation of a Proliferation-Based Expression Signature as Prognostic Marker in Early Stage Lung Adenocarcinoma

• Published in: Clinical cancer research Vol. 19; no. 22; pp. 6261 - 6271
• Main Authors: WISTUBA, Ignacio I, BEHRENS, Carmen, REID, Julia, SANGALE, Zaina, SWISHER, Steven G, KALHOR, Neda, MORAN, Cesar A, GUTIN, Alexander, LANCHBURY, Jerry S, BARBERIS, Massimo, KIM, Edward S, LOMBARDI, Francesca, WAGNER, Susanne, FUJIMOTO, Junya, RASO, M. Gabriela, SPAGGIARI, Lorenzo, GALETTA, Domenico, RILEY, Robyn, HUGHES, Elisha
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.11.2013
• Subjects: Adenocarcinoma - mortality; Adenocarcinoma - pathology; Adenocarcinoma of Lung; Aged; Antineoplastic agents; Biological and medical sciences; Biomarkers, Tumor - genetics; Cell Cycle; Cell Proliferation; Chemotherapy, Adjuvant; Female; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Male; Medical sciences; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasm Staging; Pharmacology. Drug treatments; Pneumology; Prognosis; RNA, Messenger - biosynthesis; Treatment Outcome; Tumors; Tumors of the respiratory system and mediastinum; Cell proliferation; Validation; Lung disease; Prognosis; Respiratory disease; Lung cancer; Biological marker; Early stage; Malignant tumor; Bronchopulmonary adenocarcinoma; Gene expression; Bronchopulmonary; Bronchus disease; Cancer
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.ccr-13-0596

New prognostic markers to guide treatment decisions in early stage non-small cell lung cancer are necessary to improve patient outcomes. In this report, we assess the utility of a predefined mRNA expression signature of cell-cycle progression genes (CCP score) to define 5-year risk of lung cancer-related death in patients with early stage lung adenocarcinoma. A CCP score was calculated from the mRNA expression levels of 31 proliferation genes in stage I and stage II tumor samples from two public microarray datasets [Director's Consortium (DC) and GSE31210]. The same gene set was tested by quantitative PCR in 381 formalin-fixed paraffin-embedded (FFPE) primary tumors. Association of the CCP score with outcome was assessed by Cox proportional hazards analysis. In univariate analysis, the CCP score was a strong predictor of cancer-specific survival in both the Director's Consortium cohort (P = 0.00014; HR = 2.08; 95% CI, 1.43-3.02) and GSE31210 (P = 0.0010; HR = 2.25; 95% CI, 1.42-3.56). In multivariate analysis, the CCP score remained the dominant prognostic marker in the presence of clinical variables (P = 0.0022; HR = 2.02; 95% CI, 1.29-3.17 in Director's Consortium, P = 0.0026; HR = 2.16; 95% CI, 1.32-3.53 in GSE31210). On a quantitative PCR platform, the CCP score maintained highly significant prognostic value in FFPE-derived mRNA from clinical samples in both univariate (P = 0.00033; HR = 2.10; 95% CI, 1.39-3.17) and multivariate analyses (P = 0.0071; HR = 1.92; 95% CI, 1.18-3.10). The CCP score is a significant predictor of lung cancer death in early stage lung adenocarcinoma treated with surgery and may be a valuable tool in selecting patients for adjuvant treatment.