title: A smoking-associated 7-gene signature for lung cancer diagnosis and prognosis.
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.
authors: Mary Randolph Cancer Center, West Virginia University, Morgantown, WV 26506, USA.
authors: Ying-Wooi
authors: YW
authors: Wan
authors: Rebecca A
authors: RA
authors: Raese
authors: James E
authors: JE
authors: Fortney
authors: Changchang
authors: C
authors: Xiao
authors: Dajie
authors: D
authors: Luo
authors: John
authors: J
authors: Cavendish
authors: Laura F
authors: LF
authors: Gibson
authors: Vincent
authors: V
authors: Castranova
authors: Yong
authors: Y
authors: Qian
authors: Nancy Lan
authors: NL
authors: Guo
mesh_terms: D000368:Aged; D002471:Cell Transformation, Neoplastic; D066246:ErbB Receptors / Q000096:biosynthesis; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009602:Nitrosamines / Q000494:pharmacology*; D011379:Prognosis; D016160:Retinoblastoma Protein / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D012907:Smoking / Q000009:adverse effects*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
chemical_list: D009602:Nitrosamines; D016160:Retinoblastoma Protein; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; C512478:EGFR protein, human; D066246:ErbB Receptors