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

Wistuba II, Behrens C, Lombardi F, Wagner S, Fujimoto J, Raso MG, Spaggiari L, Galetta D, Riley R, Hughes E, Reed J, Sangale Z, Swisher SG, Kahlor N, Moran C, Gutin A, Lanchbury JS, Barberis M, Kim ES.

Source

Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center.

Abstract

PURPOSE:

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 pre-defined 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.

EXPERIMENTAL DESIGN:

A CCP score was calculated from the mRNA expression levels of 31 proliferation genes in stage I and II tumors from two public microarray data sets (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.

RESULTS:

In univariate analysis the CCP score was a strong predictor of cancer-specific survival in both the DC 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 DC, 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).

CONCLUSIONS:

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.