Gene-expression signature predicts postoperative recurrence in stage I non-small cell lung cancer patients. PLoS One 2012;7(1):e30880
Date
02/01/2012Pubmed ID
22292069Pubmed Central ID
PMC3264655DOI
10.1371/journal.pone.0030880Scopus ID
2-s2.0-84856116589 (requires institutional sign-in at Scopus site) 41 CitationsAbstract
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 MMESH terms used to index this publication - Major topics in bold
AdenocarcinomaAdult
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
