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Citation
Tags
HERO ID
2347032
Reference Type
Journal Article
Title
Transcriptomic architecture of the adjacent airway field cancerization in non-small cell lung cancer
Author(s)
Kadara, H; Fujimoto, J; Yoo, SY; Maki, Y; Gower, AC; Kabbout, M; Garcia, MM; Chow, CW; Chu, Z; Mendoza, G; Shen, L; Kalhor, N; Hong, WK; Moran, C; Wang, J; Spira, A; Coombes, KR; Wistuba, II
Year
2014
Is Peer Reviewed?
Yes
Journal
Journal of the National Cancer Institute
ISSN:
0027-8874
EISSN:
1460-2105
Volume
106
Issue
3
Page Numbers
dju004
Language
English
PMID
24563515
DOI
10.1093/jnci/dju004
Abstract
BACKGROUND:
Earlier work identified specific tumor-promoting abnormalities that are shared between lung cancers and adjacent normal bronchial epithelia. We sought to characterize the yet unknown global molecular and adjacent airway field cancerization (FC) in early-stage non-small cell lung cancer (NSCLC).
METHODS:
Whole-transcriptome expression profiling of resected early-stage (I-IIIA) NSCLC specimens (n = 20) with matched tumors, multiple cytologically controlled normal airways with varying distances from tumors, and uninvolved normal lung tissues (n = 194 samples) was performed using the Affymetrix Human Gene 1.0 ST platform. Mixed-effects models were used to identify differentially expressed genes among groups. Ordinal regression analysis was performed to characterize site-dependent airway expression profiles. All statistical tests were two-sided, except where noted.
RESULTS:
We identified differentially expressed gene features (n = 1661) between NSCLCs and airways compared with normal lung tissues, a subset of which (n = 299), after gene set enrichment analysis, statistically significantly (P < .001) distinguished large airways in lung cancer patients from airways in cancer-free smokers. In addition, we identified genes (n = 422) statistically significantly and progressively differentially expressed in airways by distance from tumors that were found to be congruently modulated between NSCLCs and normal lung tissues. Furthermore, LAPTM4B, with statistically significantly increased expression (P < .05) in airways with shorter distance from tumors, was upregulated in human immortalized cells compared with normal bronchial epithelial cells (P < .001) and promoted anchorage-dependent and -independent lung cancer cell growth.
CONCLUSIONS:
The adjacent airway FC comprises both site-independent profiles as well as gradient and localized airway expression patterns. Profiling of the airway FC may provide new insights into NSCLC oncogenesis and molecular tools for detection of the disease.
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Mouse Lung Tumor Workshop 2014
Session 1 – Epidemiology and Human Pathophysiology
Human Lung Cancer
Mechanisms
Human Pathophysiology
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