Molecular subtyping reveals immune alterations associated with progression of bronchial premalignant lesions.
Nat Commun
; 10(1): 1856, 2019 04 23.
Article
em En
| MEDLINE
| ID: mdl-31015447
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Lesões Pré-Cancerosas
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Carcinoma Broncogênico
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Biomarcadores Tumorais
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Regulação Neoplásica da Expressão Gênica
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Neoplasias Pulmonares
Tipo de estudo:
Diagnostic_studies
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Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
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Screening_studies
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article