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Gene-expression signature predicts postoperative recurrence in stage I non-small cell lung cancer patients. PLoS One 2012;7(1):e30880

Date

02/01/2012

Pubmed ID

22292069

Pubmed Central ID

PMC3264655

DOI

10.1371/journal.pone.0030880

Scopus ID

2-s2.0-84856116589   31 Citations

Abstract

About 30% stage I non-small cell lung cancer (NSCLC) patients undergoing resection will recur. Robust prognostic markers are required to better manage therapy options. The purpose of this study is to develop and validate a novel gene-expression signature that can predict tumor recurrence of stage I NSCLC patients. Cox proportional hazards regression analysis was performed to identify recurrence-related genes and a partial Cox regression model was used to generate a gene signature of recurrence in the training dataset -142 stage I lung adenocarcinomas without adjunctive therapy from the Director's Challenge Consortium. Four independent validation datasets, including GSE5843, GSE8894, and two other datasets provided by Mayo Clinic and Washington University, were used to assess the prediction accuracy by calculating the correlation between risk score estimated from gene expression and real recurrence-free survival time and AUC of time-dependent ROC analysis. Pathway-based survival analyses were also performed. 104 probesets correlated with recurrence in the training dataset. They are enriched in cell adhesion, apoptosis and regulation of cell proliferation. A 51-gene expression signature was identified to distinguish patients likely to develop tumor recurrence (Dxy = -0.83, P<1e-16) and this signature was validated in four independent datasets with AUC >85%. Multiple pathways including leukocyte transendothelial migration and cell adhesion were highly correlated with recurrence-free survival. The gene signature is highly predictive of recurrence in stage I NSCLC patients, which has important prognostic and therapeutic implications for the future management of these patients.

Author List

Lu Y, Wang L, Liu P, Yang P, You M

Authors

Pengyuan Liu PhD Adjunct Professor in the Physiology department at Medical College of Wisconsin
Ming You MD, PhD Associate Provost, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adenocarcinoma
Adult
Aged
Aged, 80 and over
Biomarkers, Tumor
Carcinoma, Non-Small-Cell Lung
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Lung Neoplasms
Male
Microarray Analysis
Neoplasm Staging
Postoperative Complications
Prognosis
Recurrence
Treatment Outcome
jenkins-FCD Prod-484 8aa07fc50b7f6d102f3dda2f4c7056ff84294d1d