ArticleJTCVS open2023
Highly sensitive noninvasive early lung cancer detection using DNA methylation topology in sputum-derived epithelial cells.
Article in JTCVS open, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed, 5 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
- Long interspersed nuclear element 1 methylation in non-small cell lung cancer: implications for diagnosis, prognosis, and therapeutic targeting.Cell communication and signaling : CCS · 2025Review
- Methylated Cell-Free Tumor DNA in Sputum as a Tool for Diagnosing Lung Cancer-A Systematic Review and Meta-Analysis.Cancers · 2024Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Objective: Sputum is a source of exfoliated respiratory epithelial cells transformed early in lung carcinogenesis. Malignant cells are hypomethylated and contain less genomic 5-methylcytosine (5mC). Validating a test that recognizes and quantifies aberrantly hypomethylated cells in sputum, we assessed its potential as a screening tool for detecting early-stage non-small cell lung cancer. Methods: Cells extracted from sputum were immunofluorescence labeled with an anti-5-methylcytosine antibody and counterstained with 4',6-diamidino-2-phenylindole (DAPI) delineating global nuclear DNA (gDNA). Via confocal scanning and 3-dimensional image analysis, fluorescence 5mC and DAPI signals were measured in segmented cell nuclei, and a 5mC/DAPI co-distribution map was generated for each imaged cell. Cells were classified as hypomethylated based on 5mC load and 5mC/DAPI co-distribution. The proportion of hypomethylated epithelial cells in the sputum determines whether a patient has lung cancer. Results: A total of 88 subjects were enrolled: 12 healthy subjects; 34 high-risk subjects with benign chronic lung disorders (10 with chronic obstructive pulmonary disease, 24 with idiopathic pulmonary fibrosis), and 43 subjects with non-small cell lung cancer (27 with stage I-II and 16 with stage III-IV). The test identified early-stage non-small cell lung cancer and distinguished it from the high-risk group with 95.8% (95% confidence interval, 78.9-99.9) sensitivity and 41.2% (95% confidence interval, 24.6-59.3) specificity applying only 5mC, 95.8% (95% confidence interval, 78.9-99.9) sensitivity and 26.5% (95% confidence interval, 12.9-44.4) specificity using solely 5mC/DAPI index, and 100% (95% confidence interval, 98.7-100) sensitivity and 26.1% (95% confidence interval, 26.2-27.8) specificity with the combined parameters. Conclusions: We tested and validated a novel, noninvasive, highly sensitive screening test for non-small cell lung cancer. With the use of sputum, our test may impact lung cancer screening, evaluation of pulmonary nodules, and cancer surveillance algorithms.
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