ArticlePloS one2018
Methylation of L1RE1, RARB, and RASSF1 function as possible biomarkers for the differential diagnosis of lung cancer.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 40 citations in OpenAlex.
- Neuroendocrine tumours through an epigenetic lens: Emerging insights for diagnosis and treatment.Journal of neuroendocrinology · 2026Review
- High-Penetrance Rare Variants Underlying Familial Lung Cancer Risk: Insights From Genetic Epidemiology of Lung Cancer Consortium.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026Article
- Epigenetic mechanisms and steroid-resistant nephrotic syndrome: The future potential for SRNS diagnosis.iScience · 2026Review
- RFX2 downregulates RASSF1 expression and YAP phosphorylation through Hippo signaling to promote immune escape in lung adenocarcinoma.Cell division · 2025Article
- Molecular mechanism of genetic, epigenetic, and metabolic alteration in lung cancer.Medical oncology (Northwood, London, England) · 2025Review
- Methylation detection in percutaneous lung biopsy preservation fluid: a new strategy to improve lung cancer diagnosis.Frontiers in oncology · 2025Article
- Improving CT scan for lung cancer diagnosis with an integromic signature.Journal of biological methods · 2024Article
- Methylation-driven mechanisms of allergic rhinitis during pollen and non-pollen seasons using integrated bioinformatics analysis.Frontiers in genetics · 2024Article
- Methylated Circulating Tumor DNA in Blood as a Tool for Diagnosing Lung Cancer: A Systematic Review and Meta-Analysis.Cancers · 2023Review
- The Importance of the Immune System and Molecular Cell Signaling Pathways in the Pathogenesis and Progression of Lung Cancer.International journal of molecular sciences · 2023Review
- An Optimized CoBRA Method for the Microfluidic Electrophoresis Detection of Breast Cancer AssociatedBiotech (Basel (Switzerland)) · 2023Article
- MTA2 is one of 14 Transcription factors predicting recurrence free survival in gastric cancer and promotes cancer progression by targeting MCM5.Journal of Cancer · 2023Article
- DNA and histone modifications as potent diagnostic and therapeutic targets to advance non-small cell lung cancer management from the perspective of 3P medicine.The EPMA journal · 2022Review
- Targeting Nuclear Receptors in Lung Cancer-Novel Therapeutic Prospects.Pharmaceuticals (Basel, Switzerland) · 2022Review
- DNA methylation in pulmonary fibrosis and lung cancer.Expert review of respiratory medicine · 2022Review
- Article
- Review
- Standardization of DNA amount for bisulfite conversion for analyzing the methylation status of LINE-1 in lung cancer.PloS one · 2021Article
- Construction and Validation of a Lung Cancer Diagnostic Model Based on 6-Gene Methylation Frequency in Blood, Clinical Features, and Serum Tumor Markers.Computational and mathematical methods in medicine · 2021Article
- Comprehensive analysis of gene expression and DNA methylation data identifies potential biomarkers and functional epigenetic modules for lung adenocarcinoma.Genetics and molecular biology · 2020Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLung cancer is the major cause of cancer-related deaths worldwide. Differential diagnosis can be difficult, especially when only small samples are available. Epigenetic changes are frequently tissue-specific events in carcinogenesis and hence may serve as diagnostic biomarkers. MATERIAL AND
methods138 representative formalin-fixed, paraffin-embedded (FFPE) tissues (116 lung cancer cases and 22 benign controls) were used for targeted DNA methylation analysis via pyrosequencing of ten literature-derived methylation markers (APC, CDH1, CDKN2A, EFEMP1, FHIT, L1RE1, MGMT, PTEN, RARB, and RASSF1). Methylation levels were analyzed with the Classification and Regression Tree Algorithm (CART), Conditional Interference Trees (ctree) and ROC. Validation was performed with additional 27 lung cancer cases and 38 benign controls. TCGA data for 282 lung cancer cases was included in the analysis.
resultsCART and ctree analysis identified the combination of L1RE1 and RARB as well as L1RE1 and RASSF1 as independent methylation markers with high discriminative power between tumor and benign tissue (for each combination, 91% specificity and 100% sensitivity). L1RE1 methylation associated significantly with tumor type and grade (p<0.001) with highest methylation in the control group. The opposite was found for RARB (p<0.001). RASSF1 methylation increased with tumor type and grade (p<0.001) with strongest methylation in neuroendocrine tumors (NET).
conclusionHypomethylation of L1RE1 is frequent in tumors compared to benign controls and associates with higher grade, whereas increasing methylation of RARB is an independent marker for tumors and higher grade. RASSF1 hypermethylation was frequent in tumors and most prominent in NET making it an auxiliary marker for separation of NSCLC and NET. L1RE1 in combination with either RARB or RASSF1 could function as biomarkers for separating lung cancer and non-cancerous tissue and could be useful for samples of limited size such as biopsies.
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