Human lung tissue transcriptome: Influence of sex and age

Matteo Dugo, Chiara E. Cotroneo, Emilie Lavoie-Charland, Matteo Incarbone, Luigi Santambrogio, Lorenzo Rosso, M. van Den Berge, David Nickle, P. Pare, Yohan Bossé, Tommaso A. Dragani, Francesca Colombo

Research output: Contribution to journalArticle

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 agerelated 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.

Original languageEnglish
Article numbere0167460
JournalPLoS One
Volume11
Issue number11
DOIs
Publication statusPublished - Nov 1 2016

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ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Dugo, M., Cotroneo, C. E., Lavoie-Charland, E., Incarbone, M., Santambrogio, L., Rosso, L., van Den Berge, M., Nickle, D., Pare, P., Bossé, Y., Dragani, T. A., & Colombo, F. (2016). Human lung tissue transcriptome: Influence of sex and age. PLoS One, 11(11), [e0167460]. https://doi.org/10.1371/journal.pone.0167460