ArticleCarcinogenesis2015
Aberrant DNA methylation in non-small cell lung cancer-associated fibroblasts.
Article in Carcinogenesis, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
What it found
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Who cites it
75 citing papers in PubMed, 110 citations in OpenAlex.
- Antagonistic SMAD2/3 control of TIMP-1, VEGF-A, and hypoxia signaling in myofibroblasts shapes histotype-specific angiogenesis in lung cancer.Cell death & disease · 2026Article
- A microenvironment-determined risk continuum refines subtyping in meningioma and reveals determinants of machine learning-based tumor classification.Nature genetics · 2026Article
- Detection ofMolecular and clinical oncology · 2025Article
- Stromagenesis and cancer-associated fibroblast heterogeneity in primary tumors and metastasis: focus in non-small cell lung cancer.FEBS open bio · 2025Review
- Prognostic Potential of Cancer-Associated Fibroblast Surface Markers and Their Specific DNA Methylation in Prostate Cancer.Diagnostics (Basel, Switzerland) · 2025Article
- Epigenetic regulators in cancer therapy and progression.NPJ precision oncology · 2025Review
- Tumor suppressor genes in the tumor microenvironment.Disease models & mechanisms · 2025Review
- Micro Immune Response On-chip (MIRO) models the tumour-stroma interface for immunotherapy testing.Nature communications · 2025Article
- DDR1 as a key prognostic biomarker in non-small cell lung cancer: identification, validation, and potential therapeutic implications.Frontiers in immunology · 2025Article
- Cancer-associated fibroblasts reveal aberrant DNA methylation across different types of cancer.Clinical epigenetics · 2024Article
- Novel Semi-Nested Real-Time PCR Assay Leveraging Extendable Blocking Probes for ImprovedBiomolecules · 2024Article
- Aberrant TIMP-1 production in tumor-associated fibroblasts drives the selective benefits of nintedanib in lung adenocarcinoma.Cancer science · 2024Article
- Epigenetic regulation in cancer.MedComm · 2024Review
- Decoding the Tumour Microenvironment: Molecular Players, Pathways, and Therapeutic Targets in Cancer Treatment.Cancers · 2024Review
- Based on machine learning, CDC20 has been identified as a biomarker for postoperative recurrence and progression in stage I & II lung adenocarcinoma patients.Frontiers in oncology · 2024Article
- A novel multimodal prediction model based on DNA methylation biomarkers and low-dose computed tomography images for identifying early-stage lung cancer.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2023Article
- Diagnostic performance of RASSF1A and SHOX2 methylation combined with EGFR mutations for differentiation between small pulmonary nodules.Journal of cancer research and clinical oncology · 2023Article
- Methylation across the central dogma in health and diseases: new therapeutic strategies.Signal transduction and targeted therapy · 2023Review
- Epigenetic regulation and therapeutic targets in the tumor microenvironment.Molecular biomedicine · 2023Review
- Epigenetic regulation of cancer-associated fibroblast heterogeneity.Biochimica et biophysica acta. Reviews on cancer · 2023Review
15 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 8 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epigenetic changes through altered DNA methylation have been implicated in critical aspects of tumor progression, and have been extensively studied in a variety of cancer types. In contrast, our current knowledge of the aberrant genomic DNA methylation in tumor-associated fibroblasts (TAFs) or other stromal cells that act as critical coconspirators of tumor progression is very scarce. To address this gap of knowledge, we conducted genome-wide DNA methylation profiling on lung TAFs and paired control fibroblasts (CFs) from non-small cell lung cancer patients using the HumanMethylation450 microarray. We found widespread DNA hypomethylation concomitant with focal gain of DNA methylation in TAFs compared to CFs. The aberrant DNA methylation landscape of TAFs had a global impact on gene expression and a selective impact on the TGF-β pathway. The latter included promoter hypermethylation-associated SMAD3 silencing, which was associated with hyperresponsiveness to exogenous TGF-β1 in terms of contractility and extracellular matrix deposition. In turn, activation of CFs with exogenous TGF-β1 partially mimicked the epigenetic alterations observed in TAFs, suggesting that TGF-β1 may be necessary but not sufficient to elicit such alterations. Moreover, integrated pathway-enrichment analyses of the DNA methylation alterations revealed that a fraction of TAFs may be bone marrow-derived fibrocytes. Finally, survival analyses using DNA methylation and gene expression datasets identified aberrant DNA methylation on the EDARADD promoter sequence as a prognostic factor in non-small cell lung cancer patients. Our findings shed light on the unique origin and molecular alterations underlying the aberrant phenotype of lung TAFs, and identify a stromal biomarker with potential clinical relevance.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.