Faculty Collaboration Database

Network-based approach identified cell cycle genes as predictor of overall survival in lung adenocarcinoma patients. Lung Cancer 2013 Apr;80(1):91-8

Date

01/30/2013

Pubmed ID

23357462

Pubmed Central ID

PMC3595338

DOI

10.1016/j.lungcan.2012.12.022

Scopus ID

2-s2.0-84875252574 (requires institutional sign-in at Scopus site)   37 Citations

Abstract

Lung adenocarcinoma is the most common type of primary lung cancer. The purpose of this study was to delineate gene expression patterns for survival prediction in lung adenocarcinoma. Gene expression profiles of 82 (discovery set) and 442 (validation set 1) lung adenocarcinoma tumor tissues were analyzed using a systems biology-based network approach. We also examined the expression profiles of 78 adjacent normal lung tissues from 82 patients. We found a significant correlation of an expression module with overall survival (adjusted hazard ratio or HR=1.71; 95% CI=1.06-2.74 in discovery set; adjusted HR=1.26; 95% CI=1.08-1.49 in validation set 1). This expression module contained genes enriched in the biological process of the cell cycle. Interestingly, the cell cycle gene module and overall survival association were also significant in normal lung tissues (adjusted HR=1.91; 95% CI, 1.32-2.75). From these survival-related modules, we further defined three hub genes (UBE2C, TPX2, and MELK) whose expression-based risk indices were more strongly associated with poor 5-year survival (HR=3.85, 95% CI=1.34-11.05 in discovery set; HR=1.72, 95% CI=1.21-2.46 in validation set 1; and HR=3.35, 95% CI=1.08-10.04 in normal lung set). The 3-gene prognostic result was further validated using 92 adenocarcinoma tumor samples (validation set 2); patients with a high-risk gene signature have a 1.52-fold increased risk (95% CI, 1.02-2.24) of death than patients with a low-risk gene signature. These results suggest that a network-based approach may facilitate discovery of key genes that are closely linked to survival in patients with lung adenocarcinoma.

Author List

Li Y, Tang H, Sun Z, Bungum AO, Edell ES, Lingle WL, Stoddard SM, Zhang M, Jen J, Yang P, Wang L

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

Adenocarcinoma
Aged
Aged, 80 and over
Cell Cycle Proteins
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Gene Regulatory Networks
Humans
Lung Neoplasms
Male
Microtubule-Associated Proteins
Middle Aged
Models, Genetic
Nuclear Proteins
Oligonucleotide Array Sequence Analysis
Predictive Value of Tests
Prognosis
Survival Analysis
Time Factors
Ubiquitin-Conjugating Enzymes