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Epithelial plasticity shapes intratumoral heterogeneity and cell lineages in early-stage lung cancer - PubMed

5 days ago
  • #intratumoral heterogeneity
  • #epithelial plasticity
  • #lung cancer
  • Intratumoral heterogeneity (ITH) in early-stage lung cancer is poorly understood compared to advanced stages.
  • Single-cell and spatial transcriptomics of early-stage lung adenocarcinoma (LUAD) reveal pervasive transcriptional ITH.
  • Epithelial plasticity, including less differentiated states and transdifferentiation, drives early ITH in lung cancer.
  • Decreased differentiation is a hallmark of malignant transformation and predicts poor prognosis.
  • A unique transitional state during AT2-to-AT1 transdifferentiation shows activated tumor-suppressive pathways/genes.
  • KLF4 and JDP2 are key transcription factors that reprogram LUAD into a transitional state and inhibit progression.
  • Findings suggest potential epithelial plasticity-targeted therapies for early-stage lung cancer.