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Smoking-associated gene expression alterations in nasal epithelium reveal immune impairment linked to lung cancer risk.
de Biase, Maria Stella; Massip, Florian; Wei, Tzu-Ting; Giorgi, Federico M; Stark, Rory; Stone, Amanda; Gladwell, Amy; O'Reilly, Martin; Schütte, Daniel; de Santiago, Ines; Meyer, Kerstin B; Markowetz, Florian; Ponder, Bruce A J; Rintoul, Robert C; Schwarz, Roland F.
Afiliación
  • de Biase MS; Berlin Institute of Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Hannoversche Strasse 28, 10115, Berlin, Germany. mariastella.debiase@gmail.com.
  • Massip F; Berlin Institute of Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Hannoversche Strasse 28, 10115, Berlin, Germany. florian.massip@mines-paristech.fr.
  • Wei TT; MINES Paris, PSL University, CBIO-Centre for Computational Biology, 60 bd Saint Michel, 75006, Paris, France. florian.massip@mines-paristech.fr.
  • Giorgi FM; Institut Curie, Cedex, Paris, France. florian.massip@mines-paristech.fr.
  • Stark R; INSERM, U900, Cedex, Paris, France. florian.massip@mines-paristech.fr.
  • Stone A; Berlin Institute of Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Hannoversche Strasse 28, 10115, Berlin, Germany.
  • Gladwell A; Institute of Pathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • O'Reilly M; Cancer Research UK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge, CB2 0AY, UK.
  • Schütte D; Present Address: Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
  • de Santiago I; Cancer Research UK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge, CB2 0AY, UK.
  • Meyer KB; Papworth Trials Unit Collaboration, Department of Oncology, Royal Papworth Hospital NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, CB2 0AY, UK.
  • Markowetz F; Papworth Trials Unit Collaboration, Department of Oncology, Royal Papworth Hospital NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, CB2 0AY, UK.
  • Ponder BAJ; Cancer Research UK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge, CB2 0AY, UK.
  • Rintoul RC; Present Address: MRC Toxicology Unit, Tennis Court Road, Cambridge, CB2 1QR, UK.
  • Schwarz RF; Institute for Computational Cancer Biology (ICCB), Center for Integrated Oncology (CIO), Cancer Research Center Cologne Essen (CCCE), Faculty of Medicine and University Hospital Cologne, University of Cologne, Am Weyertal 115C, Gebäude 74, 50931, Cologne, Germany.
Genome Med ; 16(1): 54, 2024 04 08.
Article en En | MEDLINE | ID: mdl-38589970
ABSTRACT

BACKGROUND:

Lung cancer is the leading cause of cancer-related death in the world. In contrast to many other cancers, a direct connection to modifiable lifestyle risk in the form of tobacco smoke has long been established. More than 50% of all smoking-related lung cancers occur in former smokers, 40% of which occur more than 15 years after smoking cessation. Despite extensive research, the molecular processes for persistent lung cancer risk remain unclear. We thus set out to examine whether risk stratification in the clinic and in the general population can be improved upon by the addition of genetic data and to explore the mechanisms of the persisting risk in former smokers.

METHODS:

We analysed transcriptomic data from accessible airway tissues of 487 subjects, including healthy volunteers and clinic patients of different smoking statuses. We developed a computational model to assess smoking-associated gene expression changes and their reversibility after smoking is stopped, comparing healthy subjects to clinic patients with and without lung cancer.

RESULTS:

We find persistent smoking-associated immune alterations to be a hallmark of the clinic patients. Integrating previous GWAS data using a transcriptional network approach, we demonstrate that the same immune- and interferon-related pathways are strongly enriched for genes linked to known genetic risk factors, demonstrating a causal relationship between immune alteration and lung cancer risk. Finally, we used accessible airway transcriptomic data to derive a non-invasive lung cancer risk classifier.

CONCLUSIONS:

Our results provide initial evidence for germline-mediated personalized smoke injury response and risk in the general population, with potential implications for managing long-term lung cancer incidence and mortality.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pulmonares Límite: Humans Idioma: En Revista: Genome Med Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pulmonares Límite: Humans Idioma: En Revista: Genome Med Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido