Counteracting lineage-specific transcription factor network finely tunes lung adeno-to-squamous transdifferentiation through remodeling tumor immune microenvironment.

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.

SUBMITTER: Tang S 

PROVIDER: S-EPMC10084920 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature