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Molecular subtyping reveals immune alterations associated with progression of bronchial premalignant lesions
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 epithelia...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6478943/ https://www.ncbi.nlm.nih.gov/pubmed/31015447 http://dx.doi.org/10.1038/s41467-019-09834-2 |
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author | Beane, Jennifer E. Mazzilli, Sarah A. Campbell, Joshua D. Duclos, Grant Krysan, Kostyantyn Moy, Christopher Perdomo, Catalina Schaffer, Michael Liu, Gang Zhang, Sherry Liu, Hanqiao Vick, Jessica Dhillon, Samjot S. Platero, Suso J. Dubinett, Steven M. Stevenson, Christopher Reid, Mary E. Lenburg, Marc E. Spira, Avrum E. |
author_facet | Beane, Jennifer E. Mazzilli, Sarah A. Campbell, Joshua D. Duclos, Grant Krysan, Kostyantyn Moy, Christopher Perdomo, Catalina Schaffer, Michael Liu, Gang Zhang, Sherry Liu, Hanqiao Vick, Jessica Dhillon, Samjot S. Platero, Suso J. Dubinett, Steven M. Stevenson, Christopher Reid, Mary E. Lenburg, Marc E. Spira, Avrum E. |
author_sort | Beane, Jennifer E. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6478943 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-64789432019-04-25 Molecular subtyping reveals immune alterations associated with progression of bronchial premalignant lesions Beane, Jennifer E. Mazzilli, Sarah A. Campbell, Joshua D. Duclos, Grant Krysan, Kostyantyn Moy, Christopher Perdomo, Catalina Schaffer, Michael Liu, Gang Zhang, Sherry Liu, Hanqiao Vick, Jessica Dhillon, Samjot S. Platero, Suso J. Dubinett, Steven M. Stevenson, Christopher Reid, Mary E. Lenburg, Marc E. Spira, Avrum E. Nat Commun Article 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. Nature Publishing Group UK 2019-04-23 /pmc/articles/PMC6478943/ /pubmed/31015447 http://dx.doi.org/10.1038/s41467-019-09834-2 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Beane, Jennifer E. Mazzilli, Sarah A. Campbell, Joshua D. Duclos, Grant Krysan, Kostyantyn Moy, Christopher Perdomo, Catalina Schaffer, Michael Liu, Gang Zhang, Sherry Liu, Hanqiao Vick, Jessica Dhillon, Samjot S. Platero, Suso J. Dubinett, Steven M. Stevenson, Christopher Reid, Mary E. Lenburg, Marc E. Spira, Avrum E. Molecular subtyping reveals immune alterations associated with progression of bronchial premalignant lesions |
title | Molecular subtyping reveals immune alterations associated with progression of bronchial premalignant lesions |
title_full | Molecular subtyping reveals immune alterations associated with progression of bronchial premalignant lesions |
title_fullStr | Molecular subtyping reveals immune alterations associated with progression of bronchial premalignant lesions |
title_full_unstemmed | Molecular subtyping reveals immune alterations associated with progression of bronchial premalignant lesions |
title_short | Molecular subtyping reveals immune alterations associated with progression of bronchial premalignant lesions |
title_sort | molecular subtyping reveals immune alterations associated with progression of bronchial premalignant lesions |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6478943/ https://www.ncbi.nlm.nih.gov/pubmed/31015447 http://dx.doi.org/10.1038/s41467-019-09834-2 |
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