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Nat Commun. 2019 Apr 23;10(1):1856. doi: 10.1038/s41467-019-09834-2.

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

Author information

1
Boston University School of Medicine, Boston, MA, 02118, USA. jbeane@bu.edu.
2
Boston University School of Medicine, Boston, MA, 02118, USA.
3
David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA.
4
Johnson and Johnson Innovation, Cambridge, MA, 02142, USA.
5
Princeton University, Princeton, NJ, 08544, USA.
6
Kaiser Permanente, Roseville and Sacramento, Roseville, CA, USA.
7
Covance, Princeton, NJ, 08540, USA.
8
Janssen Research and Development, High Wycombe, HP12 4DP, UK.
9
Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14203, USA.

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.

PMID:
31015447
PMCID:
PMC6478943
DOI:
10.1038/s41467-019-09834-2
[Indexed for MEDLINE]
Free PMC Article

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