title: Transcriptomic Microenvironment of Lung Adenocarcinoma.
abstract: Background:Tissues surrounding tumors are increasingly studied to understand the biology of cancer development and identify biomarkers.Methods:A unique geographic tissue sampling collection was obtained from patients that underwent curative lobectomy for stage I pulmonary adenocarcinoma. Tumor and nontumor lung samples located at 0, 2, 4, and 6 cm away from the tumor were collected. Whole-genome gene expression profiling was performed on all samples (n= 5 specimens × 12 patients = 60). Analyses were carried out to identify genes differentially expressed in the tumor compared with adjacent nontumor lung tissues at different distances from the tumor as well as to identify stable and transient genes in nontumor tissues with respect to tumor proximity.Results:The magnitude of gene expression changes between tumor and nontumor sites was similar with increasing distance from the tumor. A total of 482 up- and 843 downregulated genes were found in tumors, including 312 and 566 that were consistently differentially expressed across nontumor sites. Twenty-nine genes induced and 34 knocked-down in tumors were also identified. Tumor proximity analyses revealed 15,700 stable genes in nontumor lung tissues. Gene expression changes across nontumor sites were subtle and not statistically significant.Conclusions:This study describes the transcriptomic microenvironment of lung adenocarcinoma and adjacent nontumor lung tissues collected at standardized distances relative to the tumor.Impact:This study provides further insights about the molecular transitions that occur from normal tissue to lung adenocarcinoma and is an important step to develop biomarkers in nonmalignant lung tissues.Cancer Epidemiol Biomarkers Prev; 26(3); 389-96. ©2016 AACR.
authors.affiliation: Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec, Canada. yohan.bosse@criucpq.ulaval.ca.|Department of Molecular Medicine, Laval University, Quebec, Canada.
authors.forename: Yohan
authors.initials: Y
authors.lastname: Bossé
authors.affiliation: Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec, Canada.
authors.forename: Olga
authors.initials: O
authors.lastname: Sazonova
authors.affiliation: Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec, Canada.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Gaudreault
authors.affiliation: Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec, Canada.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bastien
authors.affiliation: Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec, Canada.
authors.forename: Massimo
authors.initials: M
authors.lastname: Conti
authors.affiliation: Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec, Canada.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Pagé
authors.affiliation: Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec, Canada.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Trahan
authors.affiliation: Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec, Canada.
authors.forename: Christian
authors.initials: C
authors.lastname: Couture
authors.affiliation: Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec, Canada.|Department of Molecular Biology, Medical Biochemistry and Pathology, Laval University, Quebec, Canada.
authors.forename: Philippe
authors.initials: P
authors.lastname: Joubert
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D055785:Gene Knockdown Techniques; D006801:Humans; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000074285:Smokers / Q000706:statistics & numerical data; D059467:Transcriptome / Q000235:genetics*; D059016:Tumor Microenvironment / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor