lunes, 30 de septiembre de 2013

Validation of a Proliferation-based Expressi... [Clin Cancer Res. 2013] - PubMed - NCBI

Validation of a Proliferation-based Expressi... [Clin Cancer Res. 2013] - PubMed - NCBI

2013 Sep 18. [Epub ahead of print]

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

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.

PMID:
24048333
[PubMed - as supplied by publisher]

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