ArticleLung cancer (Amsterdam, Netherlands)2020
Identification of novel epigenetic abnormalities as sputum biomarkers for lung cancer risk among smokers and COPD patients.
Article in Lung cancer (Amsterdam, Netherlands), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Sputum Liquid Biopsy for Lung Cancer Screening, Diagnosis, Subtyping, Surveillance, Response Prediction, and Prognostication: A Scoping Review.Medical sciences (Basel, Switzerland) · 2026Article
- Novel biomarkers for lung cancer diagnosis in chronic obstructive pulmonary disease: a systematic review and metanalysis.Discover oncology · 2026Article
- Critical Biological Functions and Clinical Implications of Epigenetic-Related Candidate Biomarkers in Chronic Obstructive Pulmonary Disease: Integrated Machine Learning Screening and Basic Experimental Validation.International journal of chronic obstructive pulmonary disease · 2026Article
- Identification and Validation of Mannose Metabolism-Related Biomarkers in COPD Through Integrated Bioinformatics and Machine Learning Analysis: A Pilot Study.International journal of chronic obstructive pulmonary disease · 2026Article
- BRG1 Loss Is Frequent in Lung Cancer and Transforms Lung Epithelial Cells via Transcriptional and Epigenetic Reprograming.Cancers · 2025Article
- High-throughput Mucus Microrheology for Phenotyping and Disease Modeling.bioRxiv : the preprint server for biology · 2025Article
- DNA Methylation in Lung Cancer: Predictive Biomarkers for Effective Immunotherapy.International journal of general medicine · 2025Review
- Liquid biopsies based on DNA methylation as biomarkers for the detection and prognosis of lung cancer.Clinical epigenetics · 2022Review
- SNCA correlates with immune infiltration and serves as a prognostic biomarker in lung adenocarcinoma.BMC cancer · 2022Article
- A functional methylation signature to predict the prognosis of Chinese lung adenocarcinoma based on TCGA.Cancer medicine · 2022Article
- Identification of common microRNA between COPD and non-small cell lung cancer through pathway enrichment analysis.BMC genomic data · 2021Article
- CTNNB1 S37C mutation causing cells proliferation and migration coupled with molecular mechanisms in lung adenocarcinoma.Annals of translational medicine · 2021Article
- circ-ANXA7 facilitates lung adenocarcinoma progression via miR-331/LAD1 axis.Cancer cell international · 2021Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
objectivesSmoking is a common risk factor for chronic obstructive pulmonary disease (COPD) and lung cancer. Although COPD patients have higher risk of lung cancer compared to non-COPD smokers, the molecular links between these diseases are not well-defined. This study aims to identify genes that are downregulated by cigarette smoke and commonly repressed in COPD and lung cancer. MATERIALS AND
methodsPrimary human airway epithelial cells (HAEC) were exposed to cigarette-smoke-extract (CSE) for 10-weeks and significantly suppressed genes were identified by transcriptome array. Epigenetic abnormalities of these genes in lung adenocarcinoma (LUAD) from patients with or without COPD were determined using genome-wide and gene-specific assays and by in vitro treatment of cell lines with trichostatin-A or 5-aza-2-deoxycytidine.
resultsThe ten most commonly downregulated genes following chronic CSE exposure of HAEC and show promoter hypermethylation in LUAD were selected. Among these, expression of CCNA1, SNCA, and ZNF549 was significantly reduced in lung tissues from COPD compared with non-COPD cases while expression of CCNA1 and SNCA was further downregulated in tumors with COPD. The promoter regions of all three genes were hypermethylated in LUAD but not normal or COPD lungs. The reduced expression and aberrant promoter hypermethylation of these genes in LUAD were independently validated using data from the Cancer Genome Atlas project. Importantly, SNCA and ZNF549 methylation detected in sputum DNA from LUAD (52% and 38%) cases were more prevalent compared to cancer-free smokers (26% and 15%), respectively (p < 0.02).
conclusionsOur data show that suppression of CCNA1, SNCA, and ZNF549 in lung cancer and COPD occurs with or without promoter hypermethylation, respectively. Detecting methylation of these and previously identified genes in sputum of cancer-free smokers may serve as non-invasive biomarkers for early detection of lung cancer among high risk smokers including COPD patients.
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