ArticleDiagnostic pathology2013
Promoter methylation and expression of TIMP3 gene in gastric cancer.
Article in Diagnostic pathology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- Current evidences on XPC polymorphisms and gastric cancer susceptibility: a meta-analysis.Diagnostic pathology · 2014Pooled it
- Rewriting the Fate of Cancer: Epigenetic and Epitranscriptomic Regulators in the Metastatic Cascade.Biomolecules · 2025Review
- An Integrative Bioinformatics Approach to Investigating TIMP3 and Immune Cell Infiltration: Prognostic and Clinicopathological Implications.International journal of molecular sciences · 2025Article
- Transforming Cancer Diagnostics: The Emergence of Liquid Biopsy and Epigenetic Markers.MedComm · 2025Review
- Epigenetic regulation of TIMP-3 expression in human macrophages via physiological and pharmacological modification of histone3 lysine27 (H3K27).Molecular biology reports · 2025Article
- Tissue Inhibitor of Metalloproteinase 3: Unravelling Its Biological Function and Significance in Oncology.International journal of molecular sciences · 2024Review
- Biological and Genetic Mechanisms of COPD, Its Diagnosis, Treatment, and Relationship with Lung Cancer.Biomedicines · 2023Review
- Gene Expression Analysis of Biphasic Pleural Mesothelioma: New Potential Diagnostic and Prognostic Markers.Diagnostics (Basel, Switzerland) · 2022Article
- RNA Modifications and Epigenetics in Modulation of Lung Cancer and Pulmonary Diseases.International journal of molecular sciences · 2021Review
- Regulation of DNA methylation machinery by epi-miRNAs in human cancer: emerging new targets in cancer therapy.Cancer gene therapy · 2021Review
- The prognostic and diagnostic value of tissue inhibitor of metalloproteinases gene family and potential function in gastric cancer.Journal of Cancer · 2021Article
- The Roles of Matrix Metalloproteinases and Their Inhibitors in Human Diseases.International journal of molecular sciences · 2020Review
- Reduced Kiss‑1 expression is associated with clinical aggressive feature of gastric cancer patients and promotes migration and invasion in gastric cancer cells.Oncology reports · 2020Observational
- MAb NJ001 inhibits lung adenocarcinoma invasiveness by directly regulating TIMP-3 promoter activity via FOXP1 binding sites.Thoracic cancer · 2020Article
- Gastric Damage and Cancer-Associated Biomarkers inFrontiers in microbiology · 2020Review
- Article
- Coordinated Dialogue between UHRF1 and DNMT1 to Ensure Faithful Inheritance of Methylated DNA Patterns.Genes · 2019Review
- A Strong Decrease inFrontiers in oncology · 2019Article
- Increased TIMP-3 expression alters the cellular secretome through dual inhibition of the metalloprotease ADAM10 and ligand-binding of the LRP-1 receptor.Scientific reports · 2018Article
- The Association of BRAF V600E Mutation With Tissue Inhibitor of Metalloproteinase-3 Expression and Clinicopathological Features in Papillary Thyroid Cancer.International journal of endocrinology and metabolism · 2018Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGastric carcinoma development is a multi-stage process that involves more than one gene. Aberrant changes in DNA methylation are considered as the third mechanism that leads to anti-oncogene inactivation, which plays an essential role in tumor development. In this study, we assessed the relationship among the aberrant methylation of the promoter CpG islands of tissue inhibitor of metalloproteinase 3 (TIMP3) gene, its protein expression, and the clinicopathological features of gastric adenocarcinoma.
methodsThe methylation status of the promoter CpG islands and the protein expression of TIMP3 gene in tumors and adjacent normal mucosal tissues of 78 patients with gastric adenocarcinoma were detected by methylation-specific PCR (MSP) and immunohistochemistry.
resultsThe CpG island methylation of TIMP3 was detected in tumor tissues, cancer-adjacent tissues, and lymph nodes with metastasis. In increasing order, the hypermethylation frequency of these tissues were 35.9% (28 of 78 non-neoplastic tissues), 85% (17 of 20 early-stage cases), 89.7% (52 of 58 progressive-stage cases), and 100% (78 of 78 metastatic lymph node). A marked difference was found between tumors and non-neoplastic tissues (P<0.05), but no difference existed among the subgroups of tumors (P>0.05). Immunohistochemistry analysis confirmed TIMP3 down-regulation in tumor tissues. The rate of TIMP3 gene expression was 100% in non-neoplastic tissues but apparently decreased to various extents at different stages, i.e., decreased to 30% (6/20) at the early stage, to 3.4% (2/58) at the progressive stage, and to 0% (0/78) in metastatic lymph nodes. Among the 70 tumor tissues with negative TIMP3 expression, 64 (91.4%) were hypermethylated and 6 were unmethylated (8.6%), indicating a significant association between hypermethylation and reduced or negative TIMP3 expression (P<0.01).
conclusionThe hypermethylation of the promoter region in CpG islands is the main mechanism of TIMP3 gene expression and may provide evidence for the molecular diagnosis and stage evaluation of gastric cancer. VIRTUAL SLIDES: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1756134016954958.
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