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Gene regulatory Networks Reveal Sex Difference in Lung Adenocarcinoma.
Saha, Enakshi; Guebila, Marouen Ben; Fanfani, Viola; Fischer, Jonas; Shutta, Katherine H; Mandros, Panagiotis; DeMeo, Dawn L; Quackenbush, John; Lopes-Ramos, Camila M.
Afiliação
  • Saha E; Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.
  • Guebila MB; Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.
  • Fanfani V; Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.
  • Fischer J; Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.
  • Shutta KH; Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.
  • Mandros P; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA 02115.
  • DeMeo DL; Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.
  • Quackenbush J; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA 02115.
  • Lopes-Ramos CM; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
bioRxiv ; 2023 Sep 24.
Article em En | MEDLINE | ID: mdl-37790409
Lung adenocarcinoma (LUAD) has been observed to have significant sex differences in incidence, prognosis, and response to therapy. However, the molecular mechanisms responsible for these disparities have not been investigated extensively. Sample-specific gene regulatory network methods were used to analyze RNA sequencing data from non-cancerous human lung samples from The Genotype Tissue Expression Project (GTEx) and lung adenocarcinoma primary tumor samples from The Cancer Genome Atlas (TCGA); results were validated on independent data. We observe that genes associated with key biological pathways including cell proliferation, immune response and drug metabolism are differentially regulated between males and females in both healthy lung tissue, as well as in tumor, and that these regulatory differences are further perturbed by tobacco smoking. We also uncovered significant sex bias in transcription factor targeting patterns of clinically actionable oncogenes and tumor suppressor genes, including AKT2 and KRAS. Using differentially regulated genes between healthy and tumor samples in conjunction with a drug repurposing tool, we identified several small-molecule drugs that might have sex-biased efficacy as cancer therapeutics and further validated this observation using an independent cell line database. These findings underscore the importance of including sex as a biological variable and considering gene regulatory processes in developing strategies for disease prevention and management.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Revista: BioRxiv Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Revista: BioRxiv Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos