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A smoking-associated 7-gene signature for lung cancer diagnosis and prognosis.

Authors
Wan-Y-W; Raese-RA; Fortney-JE; Xiao-C; Luo-D; Cavendish-J; Gibson-LF; Castranova-V; Qian-Y; Guo-NL
Source
Int J Oncol 2012 Oct; 41(4):1387-1396
NIOSHTIC No.
20041238
Abstract
Smoking is responsible for 90% of lung cancer cases. There is currently no clinically available gene test for early detection of lung cancer in smokers, or an effective patient selection strategy for adjuvant chemotherapy in lung cancer treatment. In this study, concurrent coexpression with multiple signaling pathways was modeled among a set of genes associated with smoking and lung cancer survival. This approach identified and validated a 7-gene signature for lung cancer diagnosis and prognosis in smokers using patient transcriptional profiles (n=847). The smoking-associated gene coexpression networks in lung adenocarcinoma tumors (n=442) were highly significant in terms of biological relevance (network precision = 0.91, FDR<0.01) when evaluated with numerous databases containing multi-level molecular associations. The gene coexpression network in smoking lung adenocarcinoma patients was confirmed in qRT-PCR assays of the identified biomarkers and involved signaling pathway genes in human lung adenocarcinoma cells (H23) treated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Furthermore, the western blotting results of p53, phospho-p53, Rb and EGFR in NNK-treated H23 and transformed normal human lung epithelial cells (BEAS-2B) support their functional involvement in smoking-induced lung cancer carcinogenesis and progression.
Keywords
Smoking; Cancer; Lung; Lung-disease; Lung-function; Lung-disorders; Chemotherapy; Genes; Models; Tumors; Biological-function; Molecular-biology; Molecular-structure; Adenocarcinomas; Biomarkers; Humans; Carcinogens; Author Keywords: smoking; lung cancer diagnosis and prognosis; gene signature; signaling pathway; coexpression networks
Contact
Nancy Lan Guo, West Virginia University, 2816 HSS, Mary Babb Randolph Cancer Center, Morgantown, WV 26506-9300
CODEN
IJONES
Publication Date
20121001
Document Type
Journal Article
Email Address
Iguo@hsc.wv u.edu
Fiscal Year
2013
NTIS Accession No.
NTIS Price
Identifying No.
B08142012
Issue of Publication
4
ISSN
1019-6439
NIOSH Division
HELD
Priority Area
Manufacturing
Source Name
International Journal of Oncology
State
WV
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