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Counteracting lineage-specific transcription factor network finely tunes lung adeno-to-squamous transdifferentiation through remodeling tumor immune microenvironment.
- Source :
-
National science review [Natl Sci Rev] 2023 Feb 14; Vol. 10 (4), pp. nwad028. Date of Electronic Publication: 2023 Feb 14 (Print Publication: 2023). - Publication Year :
- 2023
-
Abstract
- Human lung adenosquamous cell carcinoma (LUAS), containing both adenomatous and squamous pathologies, harbors strong plasticity and is significantly associated with poor prognosis. We established an up-to-date comprehensive genomic and transcriptomic landscape of LUAS in 109 Chinese specimens and demonstrated LUAS development via adeno-to-squamous transdifferentiation. Unsupervised transcriptomic clustering and dynamic network biomarker analysis identified an inflammatory subtype as the critical transition stage during LUAS development. Dynamic dysregulation of the counteracting lineage-specific transcription factors (TFs), containing adenomatous TFs NKX2-1 and FOXA2, and squamous TFs TP63 and SOX2, finely tuned the lineage transition via promoting CXCL3/5-mediated neutrophil infiltration. Genomic clustering identified the most malignant subtype featured with STK11-inactivation, and targeting LSD1 through genetic deletion or pharmacological inhibition almost eradicated STK11-deficient lung tumors. These data collectively uncover the comprehensive molecular landscape, oncogenic driver spectrum and therapeutic vulnerability of Chinese LUAS.<br />Competing Interests: None declared.<br /> (© The Author(s) 2023. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)
Details
- Language :
- English
- ISSN :
- 2053-714X
- Volume :
- 10
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- National science review
- Publication Type :
- Academic Journal
- Accession number :
- 37051524
- Full Text :
- https://doi.org/10.1093/nsr/nwad028