Validation of a molecular and pathological model for five-year mortality risk in patients with early stage lung adenocarcinoma

Raphael Bueno, Elisha Hughes, Susanne Wagner, Alexander S. Gutin, Jerry S. Lanchbury, Yifan Zheng, Michael A. Archer, Corinne Gustafson, Joshua T. Jones, Kristen Rushton, Jennifer Saam, Edward Kim, Massimo Barberis, Ignacio Wistuba, Richard J. Wenstrup, William A. Wallace, Anne Renee Hartman, David J. Harrison

Research output: Contribution to journalArticle

Abstract

Introduction: The aim of this study was to validate a molecular expression signature [cell cycle progression (CCP) score] that identifies patients with a higher risk of cancer-related death after surgical resection of early stage (I-II) lung adenocarcinoma in a large patient cohort and evaluate the effectiveness of combining CCP score and pathological stage for predicting lung cancer mortality. Methods: Formalin-fixed paraffin-embedded surgical tumor samples from 650 patients diagnosed with stage I and II adenocarcinoma who underwent definitive surgical treatment without adjuvant chemotherapy were analyzed for 31 proliferation genes by quantitative real-time polymerase chain reaction. The prognostic discrimination of the expression score was assessed by Cox proportional hazards analysis using 5-year lung cancer-specific death as primary outcome. Results: The CCP score was a significant predictor of lung cancer-specific mortality above clinical covariates [hazard ratio (HR) = 1.46 per interquartile range (95% confidence interval = 1.12-1.90; p = 0.0050)]. The prognostic score, a combination of CCP score and pathological stage, was a more significant indicator of lung cancer mortality risk than pathological stage in the full cohort (HR = 2.01; p = 2.8 × 10-11) and in stage I patients (HR = 1.67; p = 0.00027). Using the 85th percentile of the prognostic score as a threshold, there was a significant difference in lung cancer survival between low-risk and high-risk patient groups (p = 3.8 × 10-7). Conclusions: This study validates the CCP score and the prognostic score as independent predictors of lung cancer death in patients with early stage lung adenocarcinoma treated with surgery alone. Patients with resected stage I lung adenocarcinoma and a high prognostic score may be candidates for adjuvant therapy to reduce cancer-related mortality.

Original languageEnglish
Pages (from-to)67-73
Number of pages7
JournalJournal of Thoracic Oncology
Volume10
Issue number1
DOIs
Publication statusPublished - Jan 1 2015

Keywords

  • Carcinoma
  • Nonsmall cell lung cancer
  • Real-time polymerase chain reaction
  • Risk stratification

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

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  • Cite this

    Bueno, R., Hughes, E., Wagner, S., Gutin, A. S., Lanchbury, J. S., Zheng, Y., Archer, M. A., Gustafson, C., Jones, J. T., Rushton, K., Saam, J., Kim, E., Barberis, M., Wistuba, I., Wenstrup, R. J., Wallace, W. A., Hartman, A. R., & Harrison, D. J. (2015). Validation of a molecular and pathological model for five-year mortality risk in patients with early stage lung adenocarcinoma. Journal of Thoracic Oncology, 10(1), 67-73. https://doi.org/10.1097/JTO.0000000000000365