ArticleCancer prevention research (Philadelphia, Pa.)2014
Molecular profiling of premalignant lesions in lung squamous cell carcinomas identifies mechanisms involved in stepwise carcinogenesis.
Article in Cancer prevention research (Philadelphia, Pa.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
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Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
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- Exploring lung cancer microenvironment: pathways and nanoparticle-based therapies.Discover oncology · 2025Review
- Premalignant Progression in the Lung: Knowledge Gaps and Novel Opportunities for Interception of Non-Small Cell Lung Cancer. An Official American Thoracic Society Research Statement.American journal of respiratory and critical care medicine · 2024Review
- Analysis of Methylome of Different Forms of Basal Cell Hyperplasia and Squamous Cell Metaplasia of Bronchial Epithelium.Bulletin of experimental biology and medicine · 2024Article
- USP13 drives lung squamous cell carcinoma by switching lung club cell lineage plasticity.Molecular cancer · 2023Article
- Identification of a Novel Oxidative Stress- and Anoikis-Related Prognostic Signature and Its Immune Landscape Analysis in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2023Article
- DNA methylome analysis reveals potential alterations contributing to the progression of bronchial hyperplasia.Molecular biology reports · 2023Article
- GeneRanger and TargetRanger: processed gene and protein expression levels across cells and tissues for target discovery.Nucleic acids research · 2023Article
- Cell-intrinsic differences between human airway epithelial cells from children and adults.iScience · 2022Article
- Airway basal cells show regionally distinct potential to undergo metaplastic differentiation.eLife · 2022Article
- Copy number gains of chromosome 17 identified by dual in situ hybridization in non-small cell lung cancer tissue correlate with overexpression of c-Myc.Translational cancer research · 2022Article
- Expression and Prognostic Significance of c-Myc, ALK, ROS1, BRAF, and PD-L1 Among Patients With Non-Small Cell Lung Cancer.Clinical Medicine Insights. Oncology · 2022Article
- Identification and validation of a novel ferroptosis-related gene signature for prognosis and potential therapeutic target prediction in cholangiocarcinoma.Frontiers in immunology · 2022Article
- Article
- Stem Cell-derived Respiratory Epithelial Cell Cultures as Human Disease Models.American journal of respiratory cell and molecular biology · 2021Review
- LY6K-AS lncRNA is a lung adenocarcinoma prognostic biomarker and regulator of mitotic progression.Oncogene · 2021Article
- Flow-Cytometric Analysis and Purification of Airway Epithelial-Cell Subsets.American journal of respiratory cell and molecular biology · 2021Article
- Identification of Survival-Associated Gene Signature in Lung Cancer Coexisting With COPD.Frontiers in oncology · 2021Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
Lung squamous cell carcinoma (SCC) is thought to arise from premalignant lesions in the airway epithelium; therefore, studying these lesions is critical for understanding lung carcinogenesis. Previous microarray and sequencing studies designed to discover early biomarkers and therapeutic targets for lung SCC had limited success identifying key driver events in lung carcinogenesis, mostly due to the cellular heterogeneity of patient samples examined and the interindividual variability associated with difficult to obtain airway premalignant lesions and appropriate normal control samples within the same patient. We performed RNA sequencing on laser-microdissected representative cell populations along the SCC pathologic continuum of patient-matched normal basal cells, premalignant lesions, and tumor cells. We discovered transcriptomic changes and identified genomic pathways altered with initiation and progression of SCC within individual patients. We used immunofluorescent staining to confirm gene expression changes in premalignant lesions and tumor cells, including increased expression of SLC2A1, CEACAM5, and PTBP3 at the protein level and increased activation of MYC via nuclear translocation. Cytoband enrichment analysis revealed coordinated loss and gain of expression in chromosome 3p and 3q regions, respectively, during carcinogenesis. This is the first gene expression profiling study of airway premalignant lesions with patient-matched SCC tumor samples. Our results provide much needed information about the biology of premalignant lesions and the molecular changes that occur during stepwise carcinogenesis of SCC, and it highlights a novel approach for identifying some of the earliest molecular changes associated with initiation and progression of lung carcinogenesis within individual patients.
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