Back to Search
Start Over
Altered Cell-Cycle Control, Inflammation, and Adhesion in High-Risk Persistent Bronchial Dysplasia.
- Source :
-
Cancer research [Cancer Res] 2018 Sep 01; Vol. 78 (17), pp. 4971-4983. Date of Electronic Publication: 2018 Jul 11. - Publication Year :
- 2018
-
Abstract
- Persistent bronchial dysplasia is associated with increased risk of developing invasive squamous cell carcinoma (SCC) of the lung. In this study, we hypothesized that differences in gene expression profiles between persistent and regressive bronchial dysplasia would identify cellular processes that underlie progression to SCC. RNA expression arrays comparing baseline biopsies from 32 bronchial sites that persisted/progressed to 31 regressive sites showed 395 differentially expressed genes [ANOVA, FDR ≤ 0.05). Thirty-one pathways showed significantly altered activity between the two groups, many of which were associated with cell-cycle control and proliferation, inflammation, or epithelial differentiation/cell-cell adhesion. Cultured persistent bronchial dysplasia cells exhibited increased expression of Polo-like kinase 1 (PLK1), which was associated with multiple cell-cycle pathways. Treatment with PLK1 inhibitor induced apoptosis and G <subscript>2</subscript> -M arrest and decreased proliferation compared with untreated cells; these effects were not seen in normal or regressive bronchial dysplasia cultures. Inflammatory pathway activity was decreased in persistent bronchial dysplasia, and the presence of an inflammatory infiltrate was more common in regressive bronchial dysplasia. Regressive bronchial dysplasia was also associated with trends toward overall increases in macrophages and T lymphocytes and altered polarization of these inflammatory cell subsets. Increased desmoglein 3 and plakoglobin expression was associated with higher grade and persistence of bronchial dysplasia. These results identify alterations in the persistent subset of bronchial dysplasia that are associated with high risk for progression to invasive SCC. These alterations may serve as strong markers of risk and as effective targets for lung cancer prevention. Significance: Gene expression profiling of high-risk persistent bronchial dysplasia reveals changes in cell-cycle control, inflammatory activity, and epithelial differentiation/cell-cell adhesion that may underlie progression to invasive SCC. Cancer Res; 78(17); 4971-83. ©2018 AACR .<br /> (©2018 American Association for Cancer Research.)
- Subjects :
- Adult
Aged
Biopsy
Bronchi metabolism
Bronchi pathology
Bronchial Diseases genetics
Bronchial Diseases pathology
Carcinoma, Squamous Cell pathology
Cell Cycle Checkpoints genetics
Cell Cycle Proteins genetics
Cell Proliferation genetics
Desmoglein 3 genetics
Disease Progression
Female
Gene Expression Regulation, Neoplastic
Humans
Inflammation pathology
Lung Neoplasms pathology
Male
Metaplasia
Middle Aged
Precancerous Conditions pathology
Protein Serine-Threonine Kinases genetics
Proto-Oncogene Proteins genetics
gamma Catenin genetics
Polo-Like Kinase 1
Carcinoma, Squamous Cell genetics
Inflammation genetics
Lung Neoplasms genetics
Precancerous Conditions genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1538-7445
- Volume :
- 78
- Issue :
- 17
- Database :
- MEDLINE
- Journal :
- Cancer research
- Publication Type :
- Academic Journal
- Accession number :
- 29997230
- Full Text :
- https://doi.org/10.1158/0008-5472.CAN-17-3822