title: Molecular characterization of the peripheral airway field of cancerization in lung adenocarcinoma.
abstract: Field of cancerization in the airway epithelium has been increasingly examined to understand early pathogenesis of non-small cell lung cancer. However, the extent of field of cancerization throughout the lung airways is unclear. Here we sought to determine the differential gene and microRNA expressions associated with field of cancerization in the peripheral airway epithelial cells of patients with lung adenocarcinoma. We obtained peripheral airway brushings from smoker controls (n=13) and from the lung contralateral to the tumor in cancer patients (n=17). We performed gene and microRNA expression profiling on these peripheral airway epithelial cells using Affymetrix GeneChip and TaqMan Array. Integrated gene and microRNA analysis was performed to identify significant molecular pathways. We identified 26 mRNAs and 5 miRNAs that were significantly (FDR <0.1) up-regulated and 38 mRNAs and 12 miRNAs that were significantly down-regulated in the cancer patients when compared to smoker controls. Functional analysis identified differential transcriptomic expressions related to tumorigenesis. Integration of miRNA-mRNA data into interaction network analysis showed modulation of the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) pathway in the contralateral lung field of cancerization. In conclusion, patients with lung adenocarcinoma have tumor related molecules and pathways in histologically normal appearing peripheral airway epithelial cells, a substantial distance from the tumor itself. This finding can potentially provide new biomarkers for early detection of lung cancer and novel therapeutic targets.
authors.affiliation: Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Jun-Chieh J
authors.initials: JC
authors.lastname: Tsay
authors.affiliation: Center for Health Informatics and Bioinformatics, New York University Langone Medical Center, New York, New York, United States of America.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Li
authors.affiliation: Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Ting-An
authors.initials: TA
authors.lastname: Yie
authors.affiliation: Department of Environmental Medicine, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Feng
authors.initials: F
authors.lastname: Wu
authors.affiliation: Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Segal
authors.affiliation: Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Alissa K
authors.initials: AK
authors.lastname: Greenberg
authors.affiliation: Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Eric
authors.initials: E
authors.lastname: Leibert
authors.affiliation: Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Weiden
authors.affiliation: Division of Thoracic Surgery, Department of Cardiothoracic Surgery, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Harvey
authors.initials: H
authors.lastname: Pass
authors.affiliation: Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, New York University School of Medicine, New York, New York, United States of America.
authors.forename: John
authors.initials: J
authors.lastname: Munger
authors.affiliation: Center for Health Informatics and Bioinformatics, New York University Langone Medical Center, New York, New York, United States of America; Division of Translational Medicine, Department of Medicine, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Alexander
authors.initials: A
authors.lastname: Statnikov
authors.affiliation: Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, New York University School of Medicine, New York, New York, United States of America; Department of Environmental Medicine, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Kam-Meng
authors.initials: KM
authors.lastname: Tchou-Wong
authors.affiliation: Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, New York University School of Medicine, New York, New York, United States of America; Department of Environmental Medicine, New York University School of Medicine, New York, New York, United States of America.
authors.forename: William N
authors.initials: WN
authors.lastname: Rom
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism; D000368:Aged; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics*; D012137:Respiratory System / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012907:Smoking
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger; D048049:Extracellular Signal-Regulated MAP Kinases