title: Human Lung Tissue Transcriptome: Influence of Sex and Age.
abstract: BACKGROUND
  Sex and age strongly influence the pathophysiology of human lungs, but scarce information is available about their effects on pulmonary gene expression.
  
  
  METHODS
  We followed a discovery-validation strategy to identify sex- and age-related transcriptional differences in lung.
  
  
  RESULTS
  We identified transcriptional profiles significantly associated with sex (215 genes; FDR < 0.05) and age at surgery (217 genes) in non-involved lung tissue resected from 284 lung adenocarcinoma patients. When these profiles were tested in three independent series of non-tumor lung tissue from an additional 1,111 patients, we validated the association with sex and age for 25 and 22 genes, respectively. Among the 17 sex-biased genes mapping on chromosome X, 16 have been reported to escape X-chromosome inactivation in other tissues or cells, suggesting that this mechanism influences lung transcription too. Our 22 age-related genes partially overlap with genes modulated by age in other tissues, suggesting that the aging process has similar consequences on gene expression in different organs. Finally, seven genes whose expression was modulated by sex in non-tumor lung tissue, but no age-related gene, were also validated using publicly available data from 990 lung adenocarcinoma samples, suggesting that the physiological regulatory mechanisms are only partially active in neoplastic tissue.
  
  
  CONCLUSIONS
  Gene expression in non-tumor lung tissue is modulated by both sex and age. These findings represent a validated starting point for research on the molecular mechanisms underlying the observed differences in the course of lung diseases among men and women of different ages.
authors.affiliation: Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Dugo
authors.affiliation: Department of Predictive and Preventive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Chiara E
authors.initials: CE
authors.lastname: Cotroneo
authors.affiliation: Institut Universitaire de cardiologie et de pneumologie de Québec, Québec, Canada.
authors.forename: Emilie
authors.initials: E
authors.lastname: Lavoie-Charland
authors.affiliation: Department of Surgery, San Giuseppe Hospital-MultiMedica, Milan, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Incarbone
authors.affiliation: Fondazione IRCCS Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Santambrogio
authors.affiliation: Fondazione IRCCS Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Rosso
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Pulmonology, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, The Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: van den Berge
authors.affiliation: Merck & Co. Inc., Rahway, NJ, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Nickle
authors.affiliation: University of British Columbia Center for Heart Lung Innovation and Institute for Heart and Lung Health, St. Paul's Hospital, Vancouver, BC, Canada.|Respiratory Division, Department of Medicine, The University of British Columbia, Vancouver, BC, Canada.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Paré
authors.affiliation: Institut Universitaire de cardiologie et de pneumologie de Québec, Québec, Canada.|Department of Molecular Medicine, Laval University, Québec, Canada.
authors.forename: Yohan
authors.initials: Y
authors.lastname: Bossé
authors.affiliation: Department of Predictive and Preventive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Tommaso A
authors.identifier: http://orcid.org/0000-0001-5915-4598
authors.initials: TA
authors.lastname: Dragani
authors.affiliation: Department of Predictive and Preventive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Colombo
mesh_terms: D000375:Aging / Q000235:genetics*; D005260:Female; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012727:Sex Characteristics; D014158:Transcription, Genetic; D059467:Transcriptome