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Molecular subtyping reveals immune alterations associated with progression of bronchial premalignant lesions

Author

Listed:
  • Jennifer E. Beane

    (Boston University School of Medicine)

  • Sarah A. Mazzilli

    (Boston University School of Medicine)

  • Joshua D. Campbell

    (Boston University School of Medicine)

  • Grant Duclos

    (Boston University School of Medicine)

  • Kostyantyn Krysan

    (David Geffen School of Medicine at UCLA)

  • Christopher Moy

    (Johnson and Johnson Innovation)

  • Catalina Perdomo

    (Princeton University)

  • Michael Schaffer

    (Johnson and Johnson Innovation)

  • Gang Liu

    (Boston University School of Medicine)

  • Sherry Zhang

    (Boston University School of Medicine)

  • Hanqiao Liu

    (Boston University School of Medicine)

  • Jessica Vick

    (Boston University School of Medicine)

  • Samjot S. Dhillon

    (Kaiser Permanente, Roseville and Sacramento)

  • Suso J. Platero

    (Covance)

  • Steven M. Dubinett

    (David Geffen School of Medicine at UCLA)

  • Christopher Stevenson

    (Janssen Research and Development)

  • Mary E. Reid

    (Roswell Park Comprehensive Cancer Center)

  • Marc E. Lenburg

    (Boston University School of Medicine)

  • Avrum E. Spira

    (Boston University School of Medicine
    Johnson and Johnson Innovation)

Abstract

Bronchial premalignant lesions (PMLs) are precursors of lung squamous cell carcinoma, but have variable outcome, and we lack tools to identify and treat PMLs at risk for progression to cancer. Here we report the identification of four molecular subtypes of PMLs with distinct differences in epithelial and immune processes based on RNA-Seq profiling of endobronchial biopsies from high-risk smokers. The Proliferative subtype is enriched with bronchial dysplasia and exhibits up-regulation of metabolic and cell cycle pathways. A Proliferative subtype-associated gene signature identifies subjects with Proliferative PMLs from normal-appearing uninvolved large airway brushings with high specificity. In progressive/persistent Proliferative lesions expression of interferon signaling and antigen processing/presentation pathways decrease and immunofluorescence indicates a depletion of innate and adaptive immune cells compared with regressive lesions. Molecular biomarkers measured in PMLs or the uninvolved airway can enhance histopathological grading and suggest immunoprevention strategies for intercepting the progression of PMLs to lung cancer.

Suggested Citation

  • Jennifer E. Beane & Sarah A. Mazzilli & Joshua D. Campbell & Grant Duclos & Kostyantyn Krysan & Christopher Moy & Catalina Perdomo & Michael Schaffer & Gang Liu & Sherry Zhang & Hanqiao Liu & Jessica , 2019. "Molecular subtyping reveals immune alterations associated with progression of bronchial premalignant lesions," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09834-2
    DOI: 10.1038/s41467-019-09834-2
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    Cited by:

    1. Meng Nie & Ke Yao & Xinsheng Zhu & Na Chen & Nan Xiao & Yi Wang & Bo Peng & LiAng Yao & Peng Li & Peng Zhang & Zeping Hu, 2021. "Evolutionary metabolic landscape from preneoplasia to invasive lung adenocarcinoma," Nature Communications, Nature, vol. 12(1), pages 1-13, December.

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