ArticlePloS one2013
DNA methylation profiles at precancerous stages associated with recurrence of lung adenocarcinoma.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- Prognostic and clinicopathological insights of phosphodiesterase 9A gene as novel biomarker in human colorectal cancer.BMC cancer · 2021Pooled it
- Review
- Plasma cell-free DNA methylation profile before afatinib treatment is associated with progression-free and overall survival of patients with epidermal growth factor receptor gene mutation-positive non-small cell lung cancer.Clinical epigenetics · 2025Article
- Molecular pathological approach to cancer epigenomics and its clinical application.Pathology international · 2024Review
- Non-Invasive Biomarkers for Early Lung Cancer Detection.Cancers · 2022Review
- Comparison of tumor and two types of paratumoral tissues highlighted epigenetic regulation of transcription during field cancerization in non-small cell lung cancer.BMC medical genomics · 2022Article
- DNA hypermethylation of the ZNF132 gene participates in the clinicopathological aggressiveness of 'pan-negative'-type lung adenocarcinomas.Carcinogenesis · 2021Article
- Noninvasive Diagnostics for Early Detection of Lung Cancer: Challenges and Potential with a Focus on Changes in DNA Methylation.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2020Review
- Analysis of the clinical significance of DNA methylation in gastric cancer based on a genome-wide high-resolution array.Clinical epigenetics · 2019Article
- Genome-wide DNA methylation profile of early-onset endometrial cancer: its correlation with genetic aberrations and comparison with late-onset endometrial cancer.Carcinogenesis · 2019Article
- Screening of Methylation Signature and Gene Functions Associated With the Subtypes of Isocitrate Dehydrogenase-Mutation Gliomas.Frontiers in bioengineering and biotechnology · 2019Article
- Protective potential of miR-146a-5p and its underlying molecular mechanism in diverse cancers: a comprehensive meta-analysis and bioinformatics analysis.Cancer cell international · 2019Article
- Identifying gene-gene interactions using penalized tensor regression.Statistics in medicine · 2018Article
- DNA methylation in lung tissues of mouse offspring exposed in utero to polycyclic aromatic hydrocarbons.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2017Article
- Article
- Methylated site display (MSD)-AFLP, a sensitive and affordable method for analysis of CpG methylation profiles.BMC molecular biology · 2017Article
- Genome-wide DNA methylation analysis during non-alcoholic steatohepatitis-related multistage hepatocarcinogenesis: comparison with hepatitis virus-related carcinogenesis.Carcinogenesis · 2017Article
- Genes involved in development and differentiation are commonly methylated in cancers derived from multiple organs: a single-institutional methylome analysis using 1007 tissue specimens.Carcinogenesis · 2017Article
- Methylated DNA/RNA in Body Fluids as Biomarkers for Lung Cancer.Biological procedures online · 2017Review
- Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The aim of this study was to clarify the significance of DNA methylation alterations at precancerous stages of lung adenocarcinoma. Using single-CpG resolution Infinium array, genome-wide DNA methylation analysis was performed in 36 samples of normal lung tissue obtained from patients without any primary lung tumor, 145 samples of non-cancerous lung tissue (N) obtained from patients with lung adenocarcinomas, and 145 samples of tumorous tissue (T). Stepwise progression of DNA methylation alterations from normal lung tissue to non-cancerous lung tissue obtained from patients with lung adenocarcinomas, and then tumorous tissue samples, was observed at 3,270 CpG sites, suggesting that non-cancerous lung tissue obtained from patients with lung adenocarcinomas was at precancerous stages with DNA methylation alterations. At CpG sites of 2,083 genes, DNA methylation status in samples of non-cancerous lung tissue obtained from patients with lung adenocarcinomas was significantly correlated with recurrence after establishment of lung adenocarcinomas. Among such recurrence-related genes, 28 genes are normally unmethylated (average β-values based on Infinium assay in normal lung tissue samples was less than 0.2) and their DNA hypermethylation at precancerous stages was strengthened during progression to lung adenocarcinomas (Δβ(T-N)>0.1). Among these 28 genes, we focused on 6 for which implications in transcription regulation, apoptosis or cell adhesion had been reported. DNA hypermethylation of the ADCY5, EVX1, GFRA1, PDE9A, and TBX20 genes resulted in reduced mRNA expression in tumorous tissue samples. 5-Aza-2'-deoxycytidine treatment of lung cancer cell lines restored the mRNA expression levels of these 5 genes. Reduced mRNA expression in tumorous tissue samples was significantly correlated with tumor aggressiveness. These data suggest that DNA methylation alterations at precancerous stages determine tumor aggressiveness and outcome through silencing of specific genes.
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